DIHYDROBEN2OFURANYL ALKANAMINE DERIVATIVES AS 5HT2C AGONISTS

CROSS-REFERENCE TO RELATED APPLICATIONS

This application in a Continuation in Part of co-pending United States patent application serial number 10/970,714, filed October 21 , 2004, the entirety of which is hereby incorporated herein by reference. The 10/970,714 application claims benefit under 35 U.S. C. § 119(e) to provisional application number 60/514,454, filed on October 24, 2003 which is also hereby incorporated by reference.

FIELD OF THE INVENTION The present invention relates to novel 1 -(2,3-dihydro-l -benzofuran-2- yl)alkanamine derivatives that act as agonists and partial agonists of the 5 -HT _2C receptor, processes for their preparation, and their use in medicine.

BACKGROUND OF THE INVENTION

Schizophrenia affects approximately 5 million people. The most prevalent treatments for schizophrenia are currently the 'atypical' antipsychotics, which combine dopamine (D ₂ ) and serotonin (5-HT ₂ A) receptor antagonism. Despite the reported improvements in efficacy and side-effect liability of atypical antipsychotics relative to typical antipsychotics, these compounds do not appear to adequately treat all the symptoms of schizophrenia and are accompanied by problematic side effects, such as weight gain (Allison, D. B., et. al., Am. J. Psychiatry, 156: 1686-1696, 1999; Masand, P. S., Exp. Opin. Pharmacother. I: 377-389, 2000; Whitaker, R., Spectrum Life Sciences. Decision Resources. 2:1-9, 2000).

Atypical antipsychotics also bind with high affinity to 5-HT ₂ c receptors and function as 5-HT ₂ c receptor antagonists or inverse agonists. Weight gain is a problematic side effect associated with atypical antipsychotics such as clozapine and olanzapine, and it has been suggested that 5-HT ₂ c antagonism is responsible for the increased weight gain. Conversely, stimulation of the 5-HT ₂ c receptor is known to result in decreased food intake and body weight (Walsh et. al., Psychopharmacology 124: 57-73, 1996; Cowen, P.

J., et. al., Human Psychopharmacology 10: 385-391, 1995; Rosenzweig-Lipson, S., et. al., ASPET abstract, 2000).

Several lines of evidence support a role for 5-HT _2c receptor agonism or partial agonism as a treatment for schizophrenia. Studies suggest that 5-HT ₂ c antagonists increase synaptic levels of dopamine and may be effective in animal models of

Parkinson's disease (Di Matteo, V., et. al., Neuropharmacology 37: 265-272, 1998; Fox, S. H., et. al., Experimental Neurology !5Jh 35-49, 1998). Since the positive symptoms of schizophrenia are associated with increased levels of dopamine, compounds with actions opposite to those of 5-HT ₂ c antagonists, such as 5-HT ₂ c agonists and partial agonists, should reduce levels of synaptic dopamine. Recent studies have demonstrated that 5- HT _2C agonists decrease levels of dopamine in the prefrontal cortex and nucleus accumbens (Millan, M. J., et. al., Neuropharmacology 37: 953-955, 1998; Di Matteo, V., et. al., Neuropharmacology 38: 1195-1205, 1999; Di Giovanni, G., et. al., Synapse 35: 53-61, 2000), brain regions that are thought to mediate critical antipsychotic effects of drugs like clozapine. However, 5-HT ₂ c agonists do not decrease dopamine levels in the striatum, the brain region most closely associated with extrapyramidal side effects. In addition, a recent study demonstrates that 5-HT ₂ c agonists decrease firing in the ventral tegmental area (VTA), but not in the substantia nigra. The differential effects of 5-HT ₂ c agonists in the mesolimbic pathway relative to the nigrostriatal pathway suggest that 5- HT _2C agonists have limbic selectivity, and will be less likely to produce extrapyramidal side effects associated with typical antipsychotics.

SUMMARY OF THE INVENTION

The present invention relates to certain dihydrobenzofuranyl alkanamine derivatives and to their use in medicine. In one aspect, the invention relates to novel 1- (2,3-dihydro-l-benzofuran-2-yl)alkanamine derivatives that act as agonists or partial agonists of the 5 -HT _2C receptor. The compounds can be used, for example, to treat schizophrenia and the concomitant mood disorders and cognitive impairments of schizophrenia. Compounds of the present invention are preferably less likely to produce the body weight increases associated with current atypical antipsychotics. The compounds of the present invention can also be used for the treatment of obesity and its comorbidities.

In certain embodiments, the invention relates to compounds of Formula 1:

Formula 1 or pharmaceutically acceptable salts thereof; wherein: n is 1, 2 or 3;

R and R' are, independently, hydrogen, alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 6 carbon atoms, or alkylcycloalkyl of 4 to 12 carbon atoms having 3 to 6 carbons in the cycloalkyl ring; alternatively R and R' can be taken together with the nitrogen to which they are attached to form a ring containing 2-5 carbon atoms, wherein one of the ring carbon atoms is optionally replaced by nitrogen, sulfur or oxygen; each R ¹ is independently, hydrogen, alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 6 carbon atoms, or perfluoroalkyl of 1 to 6 carbon atoms; R ² is hydrogen, alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 6 carbon atoms, or perfluoroalkyl of 1 to 6 carbon atoms;

R ^3a and R ^3b are, independently, hydrogen, halogen, hydroxyl, alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 6 carbon atoms, perfluoroalkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, or perfluoroalkoxy of 1 to 6 carbon atoms; R ⁴ , R ⁵ , R ⁶ , and R ⁷ are, independently, hydrogen, halogen, cyano, hydroxyl, carboxyl, alkyl of 1 to 8 carbon atoms, perfluoroalkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, perfluoroalkoxy of 1 to 6 carbon atoms, aryl of 5 to 10 carbon atoms, aryloxy of 5 to 10 carbon atoms, 5 to 10 membered heteroaryl having 1 to 3 heteroatoms each independently selected from nitrogen, oxygen or sulfur, alkenyl of 2 to 8 carbon atoms, alkanoyl of 2 to 6 carbon atoms, alkanoyloxy of 2 to 6 carbon atoms, carboalkoxy of 2 to 6 carbon atoms, carboxamido, alkanamido of 2 to 6 carbon atoms, alkanesulfonamido of 1 to 6 carbon atoms, amino, monoalkylamino of 1 to 6 carbon

atoms, dialkylamino of 1 to 6 carbon atoms per alkyl moiety, cycloalkyl of 3 to 8 carbon atoms, or 3 to 8 membered heterocycloalkyl having 1 to 3 heteroatoms each independently selected from nitrogen, oxygen or sulfur, wherein the cycloalkyl and heterocycloalkyl groups are saturated or partially saturated; and wherein at least one of R ⁴ , R ⁵ , R ⁶ and R ⁷ is branched alkyl of 3 to 8 carbon atoms, branched alkenyl of 3 to 8 carbon atoms, or -Y-R ⁸ , wherein Y is selected from a direct bond, lower alkylene, lower alkenylene, O, and NH and R ⁸ is aryl of 5 to 10 carbon atoms, 5 to 10 membered heteroaryl, cycloalkyl of 3 to 8 carbon atoms, or 3 to 8 membered heterocycloalkyl; and wherein any aryl, heteroaryl, cycloalkyl or heterocycloalkyl may optionally be substituted with 1 to 5 substituents independently selected from halogen, hydroxyl, cyano, alkyl of 1 to 6 carbon atoms, perfluoroalkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, or perfluoroalkoxy of 1 to 6 carbon atoms.

In certain other embodiments, the invention relates to methods for treating a patient suffering from schizophrenia, schizophreniform disorder, schizoaffective disorder, delusional disorder, substance-induced psychotic disorder, L-DOPA-induced psychosis, psychosis associated with Alzheimer's dementia, psychosis associated with Parkinson's disease, psychosis associated with Lewy body disease, dementia, memory deficit, intellectual deficit associated with Alzheimer's disease, bipolar disorders, depressive disorders, mood episodes, anxiety disorders, adjustment disorders, eating disorders, epilepsy, sleep disorders, migraines, sexual dysfunction, substance abuse, addiction to alcohol and various other drugs, including cocaine and nicotine, gastrointestinal disorders, obesity, or a central nervous system deficiency associated with trauma, stroke, or spinal cord injury that includes administering to the patient a therapeutically effective amount of a compound of formula 1, or a pharmaceutically acceptable salt thereof.

In still other embodiments, the invention relates to compositions comprising a compound of Formula 1 or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers, excipients, or diluents.

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to novel l-(2,3,-dihydro-l-benzofuran-2- yl)alkanamine derivatives that are agonists or partial agonists of the 2c subtype of brain serotonin receptors. The term "alkyl," or "alkylene," as used herein, refers to an aliphatic hydrocarbon chain having up to 8 carbon atoms, preferably 1 to 6 carbon atoms, and more preferably 1 to 4 carbon atoms. The term "alkyl" includes, but is not limited to, straight and branched chains such as methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, t-butyl, n- pentyl, isopentyl, neo-pentyl, n-hexyl, and isohexyl. In some embodiments, the alkyl group is preferably branched having 3 to 8 carbon atoms. The term "lower alkyl" refers to an alkyl group having 1 to 3 carbon atoms.

The term "alkenyl," or "alkenylene," as used herein refers to an aliphatic straight - or branched hydrocarbon chain having 2 to 8 carbon atoms that may contain 1 to 3 double bonds. Examples of alkenyl groups include vinyl, prop-1-enyl, allyl, methallyl, but-1- enyl, but-2-enyl, but-3-enyl, or 3,3-dimethylbut-l-enyl. In some embodiments, the alkenyl is preferably a branched alkenyl of 3 to 8 carbon atoms. The term "lower alkenyl" refers to an alkenyl group having 1 to 3 carbon atoms.

The term "cycloalkyl," as used herein, refers to a saturated or partially saturated, hydrocarbon ring containing 3 to 8 carbon atoms and more preferably 5 to 7 carbon atoms. Cycloalkyl groups may be monocyclic or bicyclic, and more preferably monocyclic. Bicyclic cycloalkyl groups are preferably bridged. "Bridged" refers to a cycloalkyl group that contains at least one carbon-carbon bond between two non-adjacent carbon atoms of the cycloalkyl ring. "Partially saturated" refers to a nonaromatic cycloalkyl group containing at least one double bond and preferably one double bond. Preferably, the cycloalkyl group is saturated. The cycloalkyl group may be unsubstituted or substituted as described hereinafter. The term "alkylcycloalkyl," as used herein, refers to the group -R-cycloalkyl, where cycloalkyl is as defined above and R is an alkyl moiety having 1 to 6, preferably 1 to 4, and more preferably 1 to 3 carbon atoms.

The term "heterocycloalkyl," as used herein, refers to a 3 to 8 membered, and more preferably 5 to 7 membered cycloalkyl group in which one to three carbon atoms of the cycloalkyl group are replaced with a heteroatom independently selected from oxygen, nitrogen, or sulfur. The heterocycloalkyl group may be saturated or partially saturated,

and may be monocyclic or bicyclic (such as bridged). Preferably, the heterocycloalkyl is monocyclic. The heterocycloalkyl group may be unsubstituted or substituted as described hereinafter.

The term "aryl," as used herein refers to a 5 to 10 membered carbocyclic aromatic ring. The aryl may be monocyclic or bicyclic, and may be substituted or unsubstituted. Monocyclic aryl groups preferably have 5, 6, or 7 members and bicyclic aryl groups preferably have 8, 9 or 10 members. Exemplary aryl groups include phenyl and naphthyl.

The term "aryloxy," as used herein, refers to the group Ar-O-, where Ar is an aryl group of 5 to 10 carbon atoms as previously described. The term "heteroaryl," as used herein, refers to a 5 to 10 membered monocyclic or bicyclic carbon containing aromatic ring having 1 to 3 of its ring members independently selected from nitrogen, sulfur or oxygen. Monocyclic rings preferably have 5 to 6 members and bicyclic rings preferably have 8 to 10 membered ring structures. The heteroaryl group may be unsubstituted or substituted as described hereinafter. Examples of heteroaryls include, but are not limited to, thienyl, furyl, pyrrolyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolyl, indazolyl, benzofuranyl, isobenzofuranyl, benzothienyl, isobenzothienyl, quinolyl, isoquinolyl, quinoxalinyl, or quinazolinyl.

The term "perfluoroalkyl," as used herein, refers to a straight or branched aliphatic hydrocarbon chain of 1 to 6 carbon atoms and preferably 1 to 3 carbon atoms, in which all hydrogens are replaced with fluorine.

The term "alkanamido," as used herein, refers to the group R-C(=O)-NH- where R is an alkyl group of 1 to 5 carbon atoms.

The term "alkanoyl," as used herein, refers to the group R-C(=O)- where R is an alkyl group of 1 to 5 carbon atoms.

The term "alkanoyloxy," as used herein, refers to the group R-C(=O)-O- where R is an alkyl group of 1 to 5 carbon atoms.

The term "alkanesulfonamido," as used herein, refers to the group R-S(O) ₂ -NH- where R is an alkyl group of 1 to 6 carbon atoms. The term "alkoxy," as used herein, refers to the group R-O- where R is an alkyl group of 1 to 6 carbon atoms.

The term "perfluoroalkoxy," as used herein, refers to the group R-O where R is a perfluoroalkyl group of 1 to 6 carbon atoms.

The terms "monoalkylamino" and "dialkylamino," as used herein, respectively refer to -NHR and -NRR _a , where R and R _a are independently selected from an alkyl group of 1 to 6 carbon atoms.

The term "carboxamido," as used herein, refers to the group NH ₂ -C(=O)- .

The term "carboalkoxy," as used herein, refers to the group R-O-C(K ⁾ )- where R is an alkyl group of 1 to 5 carbon atoms.

The term "carboxy," as used herein, refers to the group -COOH. The terms "halogen" or "halo," as used herein, refer to chlorine, bromine, fluorine or iodine.

The term "substituted," as used herein, refers to a moiety, such as an aryl, heteroaryl, cycloalkyl or heterocycloalkyl moiety having from 1 to about 5 substituents, and more preferably from 1 to about 3 substituents independently selected from a halogen, hydroxyl, alkyl of 1 to 6 carbon atoms, perfluoroalkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, or perfluoroalkoxy of 1 to 6 carbon atoms. Preferred substituents are a halogen atom, a lower alkyl, a perfluoroalkyl of 1 to 3 carbon atoms, an alkoxy group of 1 to 3 carbon atoms or a perfluoroalkoxy of 1 to 3 carbon atoms.

The terms "effective amount" and "therapeutically effective amount," as used herein, refer to the amount of a compound of Formula 1 that, when administered to a patient, is effective to at least partially treat a condition from which the patient is suffering from. Such conditions include, but are not limited to, schizophrenia, schizoaffective disorder, schizophreniform disorder, L-DOPA-induced psychosis, bipolar disorder, obesity, obsessive compulsive disorder, depression, panic disorder, sleep disorders, eating disorders, and epilepsy.

The term "pharmaceutically acceptable salts" or "pharmaceutically acceptable salt" refers to salts derived from treating a compound of Formula 1 with an organic or inorganic acid such as, for example, acetic, lactic, citric, cinnamic, tartaric, succinic, fumaric, maleic, malonic, mandelic, malic, oxalic, propionic, hydrochloric, hydrobromic, phosphoric, nitric, sulfuric, glycolic, pyruvic, methanesulfonic, ethanesulfonic, toluenesulfonic, salicylic, benzoic, or similarly known acceptable acids.

The term "patient," as used herein, refers to a mammal.

The terms "administer," "administering," or "administration," as used herein, refer to either directly administering a compound or composition to a patient, or administering a prodrug derivative or analog of the compound to the patient, which will form an equivalent amount of the active compound or substance within the patient's body.

The terms "treat" or "treating," as used herein, refers to partially or completely alleviating, inhibiting, preventing, ameliorating and/or relieving the condition.

The terms "suffer" or "suffering" as used herein refers to one or more conditions that a patient has been diagnosed with, or is suspected to have.

In certain embodiments, the invention relates to compounds of Formula 1:

Formula 1 or pharmaceutically acceptable salts thereof; wherein: n is 1, 2 or 3;

R and R' are, independently, hydrogen, alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 6 carbon atoms, or alkylcycloalkyl of 4 to 12 carbon atoms having 3 to 6 carbons in the cycloalkyl ring; alternatively R and R' can be taken together with the nitrogen to which they are attached to form a ring containing 2-5 carbon atoms, wherein one of the ring carbon atoms is optionally replaced by nitrogen, sulfur or oxygen; each R ¹ is independently, hydrogen, alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 6 carbon atoms, or perfluoroalkyl of 1 to 6 carbon atoms;

R ² is hydrogen, alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 6 carbon atoms, or perfluoroalkyl of 1 to 6 carbon atoms;

R ^3a and R ^3b are, independently, hydrogen, halogen, hydroxyl, alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 6 carbon atoms, perfluoroalkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, or perfluoroalkoxy of 1 to 6 carbon atoms;

R ⁴ , R ⁵ , R ⁶ , and R ⁷ are, independently, hydrogen, halogen, cyano, hydroxyl, carboxyl, alkyl of 1 to 8 carbon atoms, perfluoroalkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, perfluoroalkoxy of 1 to 6 carbon atoms, aryl of 5 to 10 carbon atoms, aryloxy of 5 to 10 carbon atoms, 5 to 10 membered heteroaryl having 1 to 3 heteroatoms each independently selected from nitrogen, oxygen or sulfur, alkenyl of 2 to 8 carbon atoms, alkanoyl of 2 to 6 carbon atoms, alkanoyloxy of 2 to 6 carbon atoms, carboalkoxy of 2 to 6 carbon atoms, carboxamido, alkanamido of 2 to 6 carbon atoms, alkanesulfonamido of 1 to 6 carbon atoms, amino, monoalkylamino of 1 to 6 carbon atoms, dialkylamino of 1 to 6 carbon atoms per alkyl moiety, cycloalkyl of 3 to 8 carbon atoms, or 3 to 8 membered heterocycloalkyl having 1 to 3 heteroatoms each independently selected from nitrogen, oxygen or sulfur, wherein the cycloalkyl and heterocycloalkyl groups are saturated or partially saturated; and wherein at least one of R ⁴ , R ⁵ , R ⁶ and R ⁷ is branched alkyl of 3 to 8 carbon atoms, branched alkenyl of 3 to 8 carbon atoms, or -Y-R ⁸ , wherein Y is selected from a direct bond, lower alkylene, lower alkenylene, O, and NH and R is aryl of 5 to 10 carbon atoms, 5 to 10 membered heteroaryl, cycloalkyl of 3 to 8 carbon atoms, or 3 to 8 membered heterocycloalkyl; and wherein any aryl, heteroaryl, cycloalkyl or heterocycloalkyl may optionally be substituted with 1 to 5 substituents independently selected from halogen, hydroxyl, cyano, alkyl of 1 to 6 carbon atoms, perfluoroalkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, or perfluoroalkoxy of 1 to 6 carbon atoms. As set forth above, R and R' are, independently, hydrogen, alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 6 carbon atoms, or alkylcycloalkyl of 4 to 12 carbon atoms having 3 to 6 carbons in the cycloalkyl ring. Alternatively R and R' can be taken together with the nitrogen to which they are attached to form a ring containing 2-5 carbon atoms, wherein one of the ring carbon atoms is optionally replaced by nitrogen, sulfur or oxygen. In some embodiments, R, R', R ¹ , and R ² are each, independently, hydrogen or alkyl of 1 to 6 carbon atoms. In certain embodiments, R' is hydrogen, and R, R ¹ , and R ² are each

independently hydrogen or alkyl of 1 to 6 carbon atoms. In certain preferred embodiments, each of R, R', R ¹ , and R ² is hydrogen.

As also set forth above, R ^3a and R ^3b may each be selected, independently, from hydrogen, halogen, hydroxyl, alkyl of 1 to 6 carbon atoms, cycloalkyl of 3 to 6 carbon atoms, perfluoroalkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, and perfluoroalkoxy of 1 to 6 carbon atoms. In certain embodiments, R ^3a and R ^3b are each independently hydrogen or alkyl of 1 to 3 carbon atoms and more preferably hydrogen.

R ⁴ , R ⁵ , R ⁶ , and R ⁷ may each be selected, independently, from hydrogen, halogen, cyano, hydroxyl, carboxyl, alkyl of 1 to 8 carbon atoms, perfluoroalkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, perfluoroalkoxy of 1 to 6 carbon atoms, aryl of 5 to 10 carbon atoms, aryloxy of 5 to 10 carbon atoms, 5 to 10 membered heteroaryl having 1 to 3 heteroatoms each independently selected from nitrogen, oxygen or sulfur, alkenyl of 2 to 8 carbon atoms, alkanoyl of 2 to 6 carbon atoms, alkanoyloxy of 2 to 6 carbon atoms, carboalkoxy of 2 to 6 carbon atoms, carboxamido, alkanamido of 2 to 6 carbon atoms, alkanesulfonamido of 1 to 6 carbon atoms, amino, monoalkylamino of 1 to 6 carbon atoms, dialkylamino of 1 to 6 carbon atoms per alkyl moiety, cycloalkyl of 3 to 8 carbon atoms, and 3 to 8 membered heterocycloalkyl having 1 to 3 heteroatoms each independently selected from nitrogen, oxygen or sulfur, wherein the cycloalkyl and heterocycloalkyl groups are saturated or partially saturated. Moreover, at least one of R ⁴ , R ⁵ , R ⁶ and R ⁷ is -Y-R ⁸ , wherein Y is selected from a direct bond, lower alkylene, lower alkenyl ene, O, and NH, and R is an aryl of 5 to 10 carbon atoms, 5 to 10 membered heteroaryl, cycloalkyl of 3 to 8 carbon atoms, 3 to 8 membered heterocycloalkyl, branched alkyl of 3 to 8 carbon atoms, or branched alkenyl of 3 to 8 carbon atoms. Additionally, where any of R ⁴ , R ⁵ , R ⁶ , and R ⁷ is aryl, heteroaryl, cycloalkyl or heterocycloalkyl, it may optionally be substituted with 1 to 5 substituents independently selected from halogen, hydroxyl, alkyl of 1 to 6 carbon atoms, perfluoroalkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, and perfluoroalkoxy of 1 to 6 carbon atoms. In certain preferred embodiments, Y is a direct bond. In certain embodiments, R ⁴ , R ⁵ , R ⁶ , and R ⁷ are preferably selected from hydrogen, halogen, alkyl of 1 to 8 carbon atoms, perfluoroalkyl of 1 to 3 carbon atoms, alkoxy of 1 to 3 carbon atoms, alkenyl of 2 to 8 carbon atoms, cycloalkyl of 3 to 8 carbon atoms, 3 to 8 membered heterocycloalkyl, aryl of 5 to 10 carbon atoms, or 5 to 10 membered

heteroaryl, provided that at least one of R ⁴ , R ⁵ , R ⁶ and R ⁷ is an aryl of 5 to 10 carbon atoms, 5 to 10 membered heteroaryl, cycloalkyl of 3 to 8 carbon atoms, 3 to 8 membered heterocycloalkyl, branched alkyl of 3 to 8 carbon atoms, or branched alkenyl of 3 to 8 carbon atoms, wherein any aryl, heteroaryl, cycloalkyl or heterocycloalkyl may optionally be substituted with 1 to 5 substituents independently selected from halogen, hydroxyl, cyano, alkyl of 1 to 6 carbon atoms, perfluoroalkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, and perfluoroalkoxy of 1 to 6 carbon atoms. Preferably, at least one of R ⁴ , R ⁵ , R ⁶ and R ⁷ and more preferably at least one of R ⁴ , R ⁵ and R ⁷ is an aryl of 5 to 10 carbon atoms, 5 to 10 membered heteroaryl, cycloalkyl of 3 to 8 carbon atoms, or 3 to 8 membered heterocycloalkyl.

In certain preferred embodiments of the invention, R ₃ R , and R are, independently, hydrogen, halogen, alkyl of 1 to 3 carbon atoms, alkoxy of 1 to 3 carbon atoms, perfluoroalkyl of 1 to 3 carbon atoms, or perfluoroalkoxy of 1 to 3 carbon atoms, and R ⁷ is a branched alkyl of 3 to 8 carbon atoms, branched alkenyl of 3 to 8 carbon atoms, cycloalkyl of 3 to 8 carbon atoms, 3 to 8 membered heterocycloalkyl, aryl of 5 to 10 carbon atoms, or 5 to 10 membered heteroaryl, wherein any aryl, heteroaryl, cycloalkyl or heterocycloalkyl may optionally be substituted with 1 to 5 substituents independently selected from halogen, hydroxyl, cyano, alkyl of 1 to 6 carbon atoms, perfluoroalkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, and perfluoroalkoxy of 1 to 6 carbon atoms. More preferably, R ⁷ is a branched alkyl of 3 to 6 carbon atoms, branched alkenyl of 3 to 6 carbon atoms, cycloalkyl of 3 to 8 carbon atoms, aryl of 5 to 10 carbon atoms, or 5 to 10 membered heteroaryl, each of which may optionally be substituted with 1 to 5 substituents independently selected from halogen, hydroxyl, alkyl of 1 to 6 carbon atoms, perfluoroalkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, and perfluoroalkoxy of 1 to 6 carbon atoms.

In other preferred embodiments of the invention, each of R ⁴ , R ⁵ and R ⁷ is, independently, aryl of 5 to 10 carbon atoms, cycloalkyl of 5 to 7 carbon atoms, or 5 to 10 membered heteroaryl, and more preferably is phenyl or napthyl, or a 5 to 10 membered heteroaryl selected from thienyl, furyl, pyrrolyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolyl, indazolyl, benzofuranyl, isobenzofuranyl, benzothienyl, isobenzothienyl, quinolyl, isoquinolyl, quinoxalinyl, or quinazolinyl, each of which may optionally be substituted

with 1 to 5 substituents independently selected from halogen, hydroxyl, alkyl of 1 to 6 carbon atoms, perfluoroalkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, and perfluoroalkoxy of 1 to 6 carbon atoms.

In certain other preferred embodiments of the invention, R ⁷ is aryl of 5 to 10 carbon atoms, cycloalkyl of 5 to 7 carbon atoms, branched alkyl of 3 to 6 carbon atoms, branched alkenyl of 3 to 6 carbon atoms, or 5 to 10 membered heteroaryl, and more preferably is phenyl or napthyl, or a 5 to 10 membered heteroaryl selected from thienyl, furyl, pyrrolyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolyl, indazolyl, benzofuranyl, isobenzofuranyl, benzothienyl, isobenzothienyl, quinolyl, isoquinolyl, quinoxalinyl, or quinazolinyl, each of which may optionally be substituted with 1 to 5 substituents independently selected from halogen, hydroxyl, alkyl of 1 to 6 carbon atoms, perfluoroalkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, and perfluoroalkoxy of 1 to 6 carbon atoms. In preferred compounds of this embodiment, R, R', R ¹ , and R ² are each, independently, hydrogen or alkyl of 1 to 6 carbon atoms.

In other preferred embodiments, R ⁷ is aryl of 5 to 10 carbon atoms, cycloalkyl of 5 to 7 carbon atoms, or 5 to 10 membered heteroaryl, or more preferably phenyl, wherein said aryl (including phenyl), cycloalkyl or heteroaryl may optionally be substituted with 1 to 5 substituents independently selected from halogen, hydroxyl, alkyl of 1 to 6 carbon atoms, perfluoroalkyl of 1 to 6 carbon atoms, alkoxy of 1 to 6 carbon atoms, and perfluoroalkoxy of 1 to 6 carbon atoms. In preferred compounds of this embodiment, at least one of R and R is halogen, alkyl of 1 to 6 carbon atoms, perfluoroalkyl of 1 to 3 carbon atoms, or alkoxy of 1 to 6 carbon atoms. Even more preferred compounds are those in which at least one of R ⁴ and R ⁵ is halogen, alkyl of 1 to 6 carbon atoms, perfluoroalkyl of 1 to 3 carbon atoms, or alkoxy of 1 to 6 carbon atoms, and R, R', R ¹ , and R ² are each, independently, hydrogen or alkyl of 1 to 6 carbon atoms. In other preferred embodiments, R ⁷ is aryl of 5 to 10 carbon atoms, optionally substituted with 1 to 3 substituents independently selected from a halogen atom, a lower alkyl, a perfluoroalkyl of 1 to 3 carbon atoms, an alkoxy group of 1 to 3 carbon atoms or a perfluoroalkoxy of 1 to 3 carbon atoms. In certain other embodiments, R ⁷ is aryl of 5 to 10 carbon atoms substituted with 1 to 3 substituents independently selected from a halogen atom, a lower alkyl, a perfluoroalkyl of 1 to 3 carbon atoms, an alkoxy group of 1

to 3 carbon atoms or a perfluoroalkoxy of 1 to 3 carbon atoms. In certain embodiments, at least one of the one to three substituents is at the ortho position of the aryl group. In certain embodiments, R ⁷ is selected from the group consisting of:

4-niethoxy-2-methylphenyl, 2-chloro-4-(trifluoromethyl)phenyl,

2-chloro-4-methoxyphenyl,

2-chloro-4-(trifluoromethoxy)phenyl,

( { 7- [4-methoxy~2-(trifluoromethyl)phenyl,

4-ethoxy-2-methylphenyl, 4-ethoxy-2-(trifluoromethyl)phenylamine,

4-chloro-2-(trifluoromethyl)phenyl,

4-fluoro-2-(trifluoromethyl)phenyl,

2-ethyl-4-methoxyphenyl,

2 ,4-dichlorophenyl, 2,4-dimethylphenyl,

4-isopropyl-2-methoxyphenyl,

4-isopropoxy-2-(trifluoromethyl)phenyl,

2-chloro-4-isopropoxyphenyl,

4-chloro-2-methylphenyl, 2,6-difluorophenyl,

2,6-dichlorophenyl,

2-chloro-6-methylphenyl,

2,4-dichlorophenyl,

2-chloro-6-fluorophenyl, 2-fluoro-6-(trifluoromethyl)phenyl,

2,6-bis(trifluoromethyl)phenyl,

2,3-dichlorophenyl,

3 -chloro-2-fluorophenyl ,

2-chloro-3-methylphenyl, 2,6-dichloro-4-methoxyphenyl, and

5-fluoro-2-methoxyphenyl.

In the compounds of the present invention, n is 1, 2 or 3, preferably 1 or 2, and more preferably 1.

In certain embodiments, the invention relates to a compound of formula 2:

2 or a pharmaceutically acceptable salt thereof, wherein: m is one or two; each of R ^2a and R ^3a is independently hydrogen, methyl, ethyl, 2-fluoroethyl, 2,2- difluoroethyl or cyclopropyl; each R ^la is independently hydrogen, halogen, OH, lower alkyl, lower alkoxy, lower haloalkyl, lower haloalkoxy, or CN; Ar is thienyl, furyl, pyridyl, or phenyl, wherein Ar is optionally substituted with one or more R ^x subsituents; each R ^x is independently selected from halogen, OH, lower alkyl, lower alkoxy, lower haloalkyl, lower haloalkoxy, or CN; and y is O, 1, 2, or 3.

In other embodiments, the invention relates to a compound of formula 2:

2 or a pharmaceutically acceptable salt thereof, wherein: m is one or two; each of R ^2a and R ^3a is independently hydrogen, methyl, ethyl, 2-fluoroethyl, 2,2- difluoroethyl or cyclopropyl; each R ^la is independently hydrogen, halogen, OH, lower alkyl, lower alkoxy, lower haloalkyl, lower haloalkoxy, or CN;

Ar is thienyl, furyl, pyridyl, or phenyl, wherein Ar is optionally substituted with one or more R ^x subsituents;

each R ^x is independently selected from halogen, OH, lower alkyl, lower alkoxy, lower haloalkyl, lower haloalkoxy, or CN; and y is 0, 1, 2, or 3; provided that: (a) at least one of R ^la is not hydrogen; or

(b) Ar is substituted with at least one R ^x group.

The compounds of formula 2, as defined above or in classes and subclasses as described herein, have affinity for and agonist or partial agonist activity at the 2c subtype of brain serotonin receptors. As defined generally above, each of the R ^2a and R ^3a groups of formula 2 is independently hydrogen, methyl, ethyl, 2-fluoroethyl, 2,2-difluoroethyl or cyclopropyl. In certain embodiments, one of the R ^2a and R ^3a groups of formula I is hydrogen and the other R ^2a or R ^3a group of formula 2 is hydrogen, methyl, ethyl, 2-fluoroethyl, 2,2- difluoroethyl or cyclopropyl. In other embodiments, neither of the R ^2a and R ^3a groups of formula 2 is hydrogen. In still other embodiments, both of the R ^2a and R ^3a groups of formula 2 are hydrogen.

As defined generally above, each R ^la group of formula 2 is independently hydrogen, halogen, OH, lower alkyl, lower alkoxy, lower haloalkyl, lower haloalkoxy, or CN. In certain embodiments, each R ^la group of formula 2 is hydrogen. In other embodiments, at least one of R ^la group of formula 2 is halogen.

According to another embodiment, y is 1 and R ^la is at the 5-position of the dihydrobenzofuran ring of formula 2, thus forming a compound of formula 2a:

2a or a pharmaceutically acceptable salt thereof, wherein each of R ^la , R ^2a , R ^3a , Ar, and m are as defined above for compounds of formula 2 and in classes and subclasses as described above and herein.

According to yet another embodiment, y is 1 and R ¹ is at the 6-position of the dihydrobenzofuran ring of formula 2, thus forming a compound of formula 2a':

2a' or a pharmaceutically acceptable salt thereof, wherein each of R ^la , R ^2a , R ^3a , Ar, and m are as defined above for compounds of formula 2 and in classes and subclasses as described above and herein.

As defined generally above, the Ar group of formula 2 is thienyl, furyl, pyridyl, or phenyl, wherein Ar is optionally substituted with one or more subsituents independently selected from halogen, OH, lower alkyl, lower alkoxy, haloalkyl, haloalkoxy, or CN. In certain embodiments, the Ar group of formula 2 is unsubstituted phenyl. In other embodiments, the Ar group of formula 2 is phenyl with at least one substituent in the ortho position. In other embodiments, the Ar group of formula 2 is phenyl with at least one substituent in the ortho position selected from halogen, lower alkyl, lower alkoxy, or trifluoromethyl. According to another aspect the present invention provides a compound of formula 2 wherein Ar is phenyl di-substituted in the ortho and meta positions with independently selected halogen lower alkyl, or lower alkoxy. Yet another aspect of the present invention provides a compound of formula 2 wherein Ar is phenyl di-subsituted in the ortho and para positions with independently selected halogen lower alkyl, or lower alkoxy. In other embodiment, the present invention provides a compound of formula 2 wherein Ar is phenyl di-subsituted in the ortho positions with independently selected halogen lower alkyl, or lower alkoxy. Exemplary substituents on the phenyl moiety of the Ar group of formula 2 include OMe, fluoro, chloro, methyl, and trifluoromethyl.

In certain embodiments, the present invention provides a compound of formula 2a' wherein Ar is phenyl with at least one substituent in the ortho position selected from halogen, lower alkyl, lower alkoxy, or trifluoromethyl. According to one embodiment, Ar is phenyl substituted with one R ^x substituent in the ortho-position, thus forming a compound of formula 2b, or with an R ^x substituent in both ortho-positions, thus forming a compound of formula 2c:

2b 2c or a pharmaceutically acceptable salt thereof, wherein each R ^la , R ^2a , R ^3a , R ^x , y and m are as defined above for compounds of formula 2 and in classes and subclasses as described above and herein.

In certain embodiments, the Ar group of formula 2 is selected from the following:

According to yet another embodiment, the present invention provides a compound of formula 2d or 2e:

2d 2e or a pharmaceutically acceptable salt thereof, wherein each R ^la , R ^2a , R ^3a , R ^x , y and m are as defined above for compounds of formula I and in classes and subclasses as described above and herein.

According to another embodiment, the present invention provides a compound of formula 2f or 2g:

2f 2g or a pharmaceutically acceptable salt thereof, wherein each R ^la , R ^2a , R ^3a , R ^x , y and m are as defined above for compounds of formula 2 and in classes and subclasses as described above and herein.

Compounds of the present invention contain asymmetric carbon atoms and thus give rise to stereoisomers, including enantiomers and diastereomers. Accordingly, it is contemplated that the present invention relates to all of these stereoisomers, as well as to mixtures of the stereoisomers. Throughout this application, the name of the product of this invention, where the absolute configuration of an asymmetric center is not indicated, is intended to embrace the individual stereoisomers as well as mixtures of stereoisomers.

In certain embodiments, the present invention provides a compound of formula 3a or 3b:

3a 3b or a pharmaceutically acceptable salt thereof, wherein each R ^la , R ^2a , R ^3a , R ^x , y and m are as defined above for compounds of formula 2 and in classes and subclasses as described above and herein.

According to another embodiment, the present invention provides a compound of formula 3c or 3d:

3c 3d or a pharmaceutically acceptable salt thereof, wherein each R la , r R>2a , r R> 3a , R , y and m are as defined above for compounds of formula 2 and in classes and subclasses as described above and herein.

In still further preferred embodiments of the invention, the compounds of Formula

1 are: (±)- 1 -(4-phenyl-2,3 -dihydro- 1 -benzofuran-2-yl)methanamine,

(+)- 1 -(4-phenyl-2,3 -dihydro- 1 -benzofuran-2-yl)methanamine,

(-)- 1 -(4-phenyl-2,3-dihydro- 1 -benzofuran-2-yl)methanamine,

(±)- 1 -[4-(2-methylphenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methanamine,

(+)-l-[4-(2-methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]m ethanamine, (-)- 1 - [4-(2-methylphenyl)-2,3 -dihydro- 1 -benzofuran-2-yl]methanamine,

(±)-(7-cyclopentyl-2,3 -dihydro- 1 -benzofuran-2-yl)methylamine,

(-)-(7-cyclopentyl-2,3-dihydro- 1 -benzofuran-2-yl)methylamine,

(+)-(7-cyclopentyl-2,3 -dihydro- l-benzofuran-2-yl)methylamine,

(±)-(5-chloro-7-cyclohexyl-2,3-dihydro-l-benzofuran-2-yl )methylamine,

(±)-N-[(5-chloro-7-cyclohexyl-2,3-dihydro-l-benzofuran-2-yl )methyl]-iV ^' -methylamine, (±)-(7-tert-butyl-5-methoxy-2,3-dihydro-l-benzofuran-2-yl)m ethylamine, (±)-(7-isopropyl-2,3-dihydro-l-benzofuran-2-yl)methylamine ₅ (-)-(7-isopropyl-2,3 -dihydro- 1 -benzofuran-2-yl)methylamine, (+)-(7-isopropyl-2,3-dihydro-l -benzofuran-2-yl)methylamine,

(±)-l-(5-chloro-7-isopropyl-4-methyl-2,3-dihydro-l-benzo furan-2-yl)methanamine, (-)-l-(5-chloro-7-isopropyl-4-methyl-2,3-dihydro-l-benzofura n-2-yl)methanamine, (+)- 1 -(5-chloro-7-isopropyl-4-methyl-2,3~dihydro- 1 -benzofuran-2-yl)methanamine, (±)-l-(7-ført-butyl-2,3-dihydro-l-benzofuran-2-yl)methanam ine, (-)- 1 -(7-tert-butyl-2,3 -dihydro- 1 -benzofuran-2-yl)methanamine, (+)- 1 -(7-tert-bxιtyl-2,3 -dihydro- 1 -benzofuran-2-yl)methanamine, (±)-l-(7-ført-butyl-5-chloro-2,3-dihydro-l-benzofuran-2-yl )methanamine, (-)- 1 -(7-tert-bvLty\-5 -chloro-2,3 -dihydro- 1 -benzofuran-2-yl)methanamine, (+)-l-(7-tert-butyl-5-chloro-2,3-dihydro-l-benzofuran-2-yl)m ethanamine, (±)-(6-phenyl-2,3-dihydro- 1 -benzofuran-2-yl)methanamine,

(±)-l-{7-[3,5-bis(trifluoromethyl)phenyl]-2,3-dihydro-l- benzofuran-2-yl}methanamine,

(d=)- 1 -[7-(I -naphthyl)-2,3-dihydro- 1 -benzofuran-2-yl]methanamine,

(±)- 1 -[7-(3-chloro-4-fluorophenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methanamine,

(d=)-l-[7-(3,5-dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl ]methanamine, (±)-l-(7-phenyl-2,3-dihydro-l-benzofuran-2-yl)methanamine, (+)-( 1 -(7 -phenyl-2,3 -dihydro- 1 -benzofuran-2-yl)methanamine, (-)- 1 -(7-phenyl-2,3-dihydro- 1 -benzofuran-2-yl)methanamine, (±)-l-[7-(2-naphthyl)-2,3-dihydro-l-benzofuran-2-yl]methana mine, (±)-l-(2',3'-dihydro-2,7'-bi-l-benzofuran-2'-yl)methanamine , (±)- 1 - [7-(3 -methylphenyl)-2,3 -dihydro- 1 -benzofuran-2-yl]methanamine, (+)-l-[7-(3-methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]meth anamine, (-)-l-[7-(3-methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]meth anamine, (±)-l-(7-thien-3-yl-2,3-dihydro-l-benzofuran-2-yl)methanami ne, (+)- 1 -(7-thien-3-yl-2,3-dihydro- 1 -benzofuran-2-yl)methanamine ₅ (-)-l-(7-thien-3-yl-2,3-dihydro-l-benzofuran-2-yl)methanamin e,

(±)-l-[7-(2-methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]met hanamine, (+)- 1 -[7-(2-methylphenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methanamine ₃

(-)- 1 -[7-(2-methylphenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methanamine, (±)-l-[7-(2-fluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]met hanamine, (+)-l-[7-(2-fluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]niet hanamine, (-)-l-[7-(2-fluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]meth anamine, (±)-l-{7-[2-(trifluoromethyl)phenyl]-2,3-dihydro-l-benzofur an-2-yl}methanamine, (-)- 1 -{7-[2-(trifluoromethyl)phenyl]-2,3-dihydro- 1 -benzofuran-2-yl}methanamine, (+)-l-{7-[2-(trifluoromethyl)phenyl]-2,3-dihydro-l-benzofura n-2-yl}methanamine, (±)- 1 - [7-(2,6-dimethylphenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methanamine, (-)-l-[7-(2,6-dimethylphenyl)-2,3-dihydro-l-benzofiiran-2-yl ]methananiine, (+)-l-[7-(2,6-dimethylphenyl)-2,3-dihydro-l-benzofuran-2-yl] methanamine, (±)- 1 - [7-(2-methoxyphenyl)-2,3 -dihydro- 1 -benzofuran-2-yl]methanamine, (±)- 1 - [7-(2-chlorophenyl)-2,3 -dihydro- 1 -benzofuran-2-yl]methanamine, (±)-[7-(2-isopropylphenyl)-2,3-dihydro-l-benzofuran-2-yl]me thylamine, (+)-[7-(2-isopropylphenyl)-2,3-dihydro-l-benzofuran-2-yl]met hylamine, (-)-[7-(2-isopropylphenyl)-2,3-dihydro-l -benzofuran-2-yl]methylamine, (±)-l-[7-(3-fluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]met hanamine, (d=)-l-[7-(3-chlorophenyl)-2,3-dihydro-l-benzofiiran-2-yl]me thanamine, (+)-l-[7-(3-chlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]meth anamine, (-)-l-[7-(3-chlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]meth anamine, (±)- 1 -[7-(3-methoxyphenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methanamine,

(±)-l-{7-[3-(trifluoromethyl)phenyl]-2,3-dihydro-l-benzofor an-2-yl}methanamine, (±)-l-[7-(4-methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]met hanamine, (+)-l-[7-(4-methylphenyl)-2,3-dihydro-l-benzofαran-2-yl]met hanamine, (-)-l-[7-(4-methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]meth anamine, (±)-l-[7-(4-fluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]met hanamine, (+)- 1 - [7-(4-fluorophenyl)-2,3 -dihydro- 1 -benzofuran-2-yl]methanamine, (-)-l-[7-(4-fluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]meth anamine, (±)-l-[7-(4-chlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]met hanamine, (+)- 1 -[7-(4-chlorophenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methanamine, (-)-l-[7-(4-chlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]meth anamine ₃ (±)- 1 - [7-(4-methoxyphenyl)-2,3 -dihydro- 1 -benzofuran-2-yl]methanamine, (+)-l-[7-(4-methoxyphenyl)-2,3-dihydro-l-benzofuran-2-yl]met hanamine,

(-)-l-[7-(4-methoxyphenyl)-2,3-dihydro-l-benzofuran-2-yl]met hanamine, (±)-l-{7-[4-(trifluoromethyl)phenyl]-2,3-dihydro-l-benzofur an-2-yl}methanamine, (±)-l-[7-(2,4-dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl ]methanamine, (±)- 1 -(5-chloro-7-phenyl-2,3-dihydro- 1 -benzofuran-2-yl)methanamine, (+)- 1 -(5-chloro-7-phenyl-2,3-dihydro- 1 -benzofuran-2-yl)methanamine, (-)-l-(5-chloro-7-phenyl-2,3-dihydro-l-benzofuran-2-yl)metha namine, (±)-l-[5-chloro-7-(2-chlorophenyl)-2,3-dihydro-l-benzofuran -2-yl]methanamine, (±)-l-[5-chloro-7-(3-methylphenyl)-2,3-dihydro-l-benzofuran -2-yl]methanamine, (±)-l-[5-chloro-7-(3-chlorophenyl)-2,3-dihydro-l-benzofuran -2-yl]methanamine ₅ (±)-(5-chloro-7-thien-3-yl-2,3-dihydro- 1 -benzofuran-2-yl)methylamine, (-)-(5-chloro-7-thien-3-yl-2,3-dihydro-l-benzofuran-2-yl)nie thylamine, (+)-(5-chloro-7-thien-3-yl-2,3-dihydro-l-benzofuran-2-yl)met hylamine, (+)-N-[(5-chloro-7-thien-3-yl-2,3-dihydro-l-benzofuran-2-yl) methyl]-iV-nietliylamine, (-)-iV- [(5-chloro-7-thien-3 -yl-2,3 -dihydro- 1 -benzofuran-2-yl)methyl] -N-methylamine, (±)-l-[5-chloro-7-(2-methylphenyl)-2,3-dihydro-l-benzofuran -2-yl]methanamine, (+)- 1 -[5-chloro-7-(2-methylphenyl)-2,3-dihydro- 1 -benzofiιran-2-yl]methanamine, (-)-l-[5-chloro-7-(2-methylphenyl)-2,3-dihydro-l-benzofuran- 2-yl]methanamine, (±)- 1 -(4-fluoro-7-phenyl-2,3 -dihydro- 1 -benzofuran-2-yl)methanamine, (±)- 1 -[4-fluoro-7-(2-methylphenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methanamine, (±)-l-[7-(2-chlorophenyl)-5-fluoro-2,3-dihydro-l-benzofuran -2-yl]methanamine, (+)-l-[7-(2-chlorophenyl)-5-fluoro-2,3-dihydro-l-benzofuran- 2-yl]methanamine, (-)-l-[7-(2-chlorophenyl)-5-fluoro-2,3-dihydro-l-benzofuran- 2-yl]methanamine, (±)-l-(5-fluoro-7-phenyl-2,3-dihydro-l-benzofuran-2-yl)meth anamine, (±)- 1 -[5-fluoro-7-(2-methylphenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methanamine, (+)-l -[5-fluoro-7-(2-methylphenyl)-2,3-dihydro-l -benzofuran-2-yl]methanamine, (-)-l-[5-fluoro-7-(2-methylphenyl)-2,3-dihydro-l-benzofuran- 2-yl]methanamine, (±)-l-[5-fluoro-7-(2-fluorophenyl)-2,3-dihydro-l-benzofuran -2-yl]methanamine , (±)- 1 - { 5-fluoro-7- [2-(trifluoromethyl)phenyl] -2,3-dihydro- 1 -benzofuran-2- yl}methanamine, (±)-(4,5-difluoro-7-phenyl-2,3-dihydro-l-benzofuran-2-yl)me thylamine,

(±)- 1 -[4,5-difluoro-7-(2-methylphenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methanamine, (±)- 1 -(5 -chloro-2-methyl-7-phenyl-2,3-dihydro- 1 -benzofuran-2-yl)methanamine,

(±)-(5-chloro-2-methyl-7-thien-3-yl-2,3-dihydro-l-benzofura n-2-yl)methylamine, (±)-(5-chloro-2-methyl-7-thien-2-yl-2,3-dihydro-l-benzofura n-2-yl)methylaniine, (-)-l-(7-tert-butyl-5-methoxy-2 ₅ 3-dihydro-l-benzofuran-2-yl)methanamine, (+)-l-(7-tert-butyl-5-methoxy-2,3-dihydro-l-benzofuran-2-yl) methanamine, (±)-l-{7-[(lE)-3,3-dimethylbut-l-enyl]-2,3-dihydro-l-benzof uran-2-yl}methanamine ₃ (±)-l-[7-(3,3-dimethylbutyl)-2,3-dihydro-l-benzofuran-2-yl] methanamine, (±)- 1 - [4-(4-methy lphenyl)-2,3 -dihydro- 1 -benzofuran-2-yl] methanamine, (±)- 1 - {4- [2-(trifluoromethyl)phenyl] -2,3 -dihydro- 1 -benzofuran-2-yl } methanamine, (-)- 1 - {4-[2-(trifluoromethyl)phenyl] -2,3 -dihydro- 1 -benzofuran-2-yl } methanamine, (+)-l-{4-[2-(trifluoromethyl)phenyl]-2,3-dihydro-l-benzofura n-2-yl}methanamine, (±)-l-[4-(2,6-dimethylphenyl)-2,3-dihydro-l-benzofuran-2-yl ]methanamine, (+)-l-[4-(2,6-dimethylphenyl)-2,3-dihydro-l-benzofuran-2-yl] methanamine, (-)-l-[4-(2,6-dimethylphenyl)-2,3-dihydro-l-benzofuran-2-yl] methanamine, (+)-l-[7-(2-methoxyphenyl)-2,3-dihydro-l-benzofuran-2-yl]met hanamine, (-)-l -[7-(2-chlorophenyl)~2,3~dihydro~l -benzofuran-2-yl]methanamine, (+)-l-[7-(2-chlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]meth anamine, (+)-l-[7-(3-fluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]meth anamine, (-)-l-[7-(3-fluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]meth anamine, (+)-l-[7-(3-methoxyphenyl)-2,3-dihydro-l-benzofuran-2-yl]met hanamine, (-)-l-[7-(3-methoxyphenyl)-2,3-dihydro-l-benzofuran-2-yl]met hanamine,

(-)- 1 - { 7- [3 -(trifluoromethyl)phenyl] -2,3-dihydro- 1 -benzofuran-2-yl } methanamine, (+)-l-{7-[3-(trifluoromethyl)phenyl]-2,3-dihydro-l-benzofura n-2-yl}methanamine, (+)-l-{7-[4-(trifluoromethyl)phenyl]-2,3-dihydro-l-benzofura n-2-yl}methanamine, (-)- 1 - { 7- [4-(trifluoromethyl)phenyl] -2,3-dihydro- 1 -benzofuran-2-yl} methanamine, (±)-l-[7-(2,6-difluorophenyl)-2,3-dihydro-l-benzofuran-2-yl ]methanamine, (±)-l-[7-(2,6-dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl ]methanamine, (-)-l-[7-(2,6-dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl] methanamine, (+)-l-[7-(2,6-dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl] methanamine, (±)-l-[7-(2,4-dimethoxyphenyl)-2,3-dihydro-l-benzofuran-2-y l]methanamine, (-)-l -[7-(2,4-dimethoxyphenyl)-2,3-dihydro-l -benzofuran-2-yl]methanamine, (+)- 1 ~[7-(2,4-dimethoxyphenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methanamine, (±)-l-[7-(2,4-difluorophenyl)-2,3-dihydro-l-benzofuran-2-yl ]methanamine,

(+)- 1 - [7-(2,4-difluorophenyl)-2,3 -dihydro- 1 -benzofuran-2-yl] methanamine, (-)-l-[7-(2,4-difluorophenyl)-2,3-dihydro-l-benzofuran-2-yl] methananiine, (-)-l-[7-(2,4-dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl] methanamine, (+)-l-[7-(2,4-dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl] methanamine, (-)-l-{5-fluoro-7-[2-(trifluoromethyl)phenyl]-2,3-dihydro-l- benzofuran-2- y 1 } methanamine ,

(+)-l-{5-fluoro-7-[2-(trifluoromethyl)phenyl]-2,3-dihydro-l- benzofuran-2- yl} methanamine, (±)- 1 -(7-benzyl-2,3 -dihydro- 1 -benzofuran-2-yl)methanamine, (+)- 1 -(7-benzyl-2,3-dihydro- 1 -benzofuran-2-yl)methanamine, (-)-l-(7-benzyl-2,3-dihydro-l~benzofuran-2-yl)methanamine, (±)-l-{7-[(E)-2-phenylvinyl]-2,3-dihydro-l-benzofuran-2-yl} methanamine, or (±)-l-[7-(2-phenylethyl)-2 ₅ 3-dihydro-l-benzofuran-2-yl]methanamine, or a pharmaceutically acceptable salt thereof. In other preferred embodiments of the invention, the compounds of Formula 1 are:

2(±)- 1 - [7-(2,3 -dimethylphenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methanamine, (±)-{[7-(2,3-dimethoxyphenyl)-2,3-dihydro-l-benzofuran-2-yl ]methyl}amine, (-)-{[(7-(2,3-dimethoxyphenyl)-2,3-dihydro-l-benzofuran-2-yl ]methyl}amine, (+)- { [(7-(2,3-dimethoxyphenyl)-2,3-dihydro- 1 -benzofuran-2-yl] methyl} amine, (+)- { [7-(4-chloro-2-methylphenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methyl} amine, (-)- { [7-(4-chloro-2-methylphenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methyl} amine, (±)-{[7-(2,3-difluorophenyl)-2,3-dihydro-l-benzofuran-2-yl] methyl}amine, (±)-{[7-(2,5-dimethylphenyl)-2,3-dihydro-l-benzofuran-2-yl] methyl}amine, (±)-{[7-(2,5-dimethoxyphenyl)-2,3-dihydro-l-benzofuran-2-yl ]methyl}amine, (±)-{[7-(2,5-dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl] methyl}amine, (+)-{[7-(2,5-dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]m ethyl}amine, (-)-{[7-(2,5-dichlorophenyl)-2,3-dihydro-l-benzofuran~yl]met hyl}amine, (±)-{[7-(2,4,6-trichlorophenyl)-2,3-dihydro-l-benzofuran-2- yl]methyl}amine, (±)- { [7-(4-chloro-2-methylphenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methyl} amine, (±)-{ [7-(5-chloro-2-methylphenyl)-2,3-dihydro- 1 -benzofuran-2-yl] methyl} amine, (±)-{[7-(5-chloro-2-methoxyphenyl)-2,3-dihydro-l-benzofuran -2-yl]methyl}amine, (±)-[(7-pyridin-3-yl-2,3-dihydro-l-benzofuran-2-yl)methyl]a mine,

(+)-{[7-pyridin-3-yl-2,3-dihydro-l-benzoftιran-2-yl]meth yl}amine, (-)-{[7-pyridin-3-yl-2,3-dihydro-l-benzofuran-2-yl]methyl}am ine, (±)-N-[2-(aminomethyl)-2,3-dihydro-l-benzofuran-7-yl]-N-phe nylamine, (±)-N-[2-(aminomethyl)-2,3-dihydro-l-benzofuran-7-yl]-N-(4- methylphenyl)amine, (±)-N-[2-(aminomethyl)-2,3-dihydro-l-benzofuran-7-yl]-N-(4- chlorophenyl)aniine, (±)-N-[2-(aminomethyl)-2,3-dihydro-l-benzofuran-7-yl]-N-(4- methoxyphenyl)amine, (±)-N- [2-(aminomethyl)-2,3 -dihydro- 1 -benzofuran-7-yl] -N-[4-

(trifluoromethyl)phenyl] amine,

(±)-N- [2-(aminomethyl)-2,3 -dihydro- 1 -benzofuran-7-yl] -N-(4-fluorophenyl)amine, (±)-N- [2-(aminomethyl)-2,3 -dihydro- 1 -benzofuran-7-yl] -N-(3,4-dichlorophenyl)amine, (±)-N-[2-(aminomethyl)-2,3-dihydro-l-benzofuran-7-yl]-N-(2, 4-dimethylphenyl)amine, (±)-N- [2-(aminomethyl)-2,3-dihydro- 1 -benzofuran-7-yl] -N-(3 ,4-dimethylphenyl)amine, (±)-N- [2-(aminomethyl)-2,3-dihydro- 1 -benzofuran-7-yl] -N-(3 -methylphenyl)amine, (±)-N-[2-(aminomethyl)-2,3-dihydro-l-benzofuran-7-yl]-N-(3- fluorophenyl)amine, (±)-N-2-(aminomethyl)-N- [3 -(trifluoromethyl)phenyl] -2,3-dihydro- 1 -benzofuran-7- amine, (±)-N- [2-(aminomethyl)-2,3-dihydro- 1 -benzofuran-7-yl] -N-(4-methoxy-3 - methylphenyl)amine,

(±)-N-[2-(aminomethyl)-2,3-dihydro-l-benzofuran-7-yl]-N- (3,5-difluorophenyl)amine, (±)-N-[2-(aminomethyl)-2,3-dihydro-l-benzofuran-7-yl]-N-(3- trifluoromethoxy)phenyl] amine, (±)-N-[2-(aminomethyl)-2,3-dihydro-l-benzofuran-7-yl]-N-(3- chloro-4- methylphenyl)amine,

(±)-N-[2-(aminomethyl)-2,3-dihydro-l-benzofuran-7-yl]-N- (3,5-dichlorophenyl)amine, (±)-N-[2-(aminomethyl)-2,3-dihydro-l-benzofuran-7-yl]-N-(3- chlorophenyl)amine, (±)-N-[2-(aminomethyl)-2,3-dihydro-l-benzofuran-7-yl]-N-(4- chloro-3- methylphenyl)amine,

(±)-N-[2-(aminomethyl)-2,3-dihydro-l-benzofuran-7-yl]-N-(3, 5-dimethylphenyl)amine, (±)-N-[2-(aminomethyl)-2 ₅ 3-dihydro-l-benzofuran-7-yl]-N-(3-chloro-4- fluorophenyl)amine,

(±)-N-[2-(aminomethyl)-2,3-dihydro-l-benzofuran-7-yl]-N- (2-fluorophenyl)amine, (±)- { [5-fluoro-7-(2-methoxyphenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methyl} amine,

(±)- { [5-fluoro-7-(3-fluorophenyl)-2,3-dihydro- 1 -benzofuran-2-yl] methyl} amine, (±)-{[5-fluoro-7-(3-methoxyphenyl)-2,3-dihydro-l-benzofuran -2-yl]methyl}amine, (±)-{[5-fluoro-7-(3-methylphenyl)-2,3-dihydro-l-benzofuran- 2-yl]methyl}amine, (±)-{[5-fluoro-7-(4-fluorophenyl)-2,3-dihydro-l-benzofuran- 2-yl]methyl}amine, (±)-{[5-fluoro-7-(4-chlorophenyl)-2,3-dihydro-l-benzofuran- 2-yl]methyl}amine, (±)- { [5-fluoro-7-(4-methylphenyl)-2,3-dihydro- 1 -benzofuran-2-yl] methyl} amine, (±)- { [5-fluoro-7-(4-methoxyphenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methyl} amine, (±)-[(5-fluoro-7-thien-3-yl-2,3-dihydro-l-benzofuran-2-yl)m ethyl]amine, (±)- { [5 -fluoro-7-(3 -furyl)-2,3 -dihydro- 1 -benzofuran-2-yl] methyl } amine, (±)-[(5-fluoro-7-pyridin-2-yl-2,3-dihydro-l-benzofuran-2-yl )methyl]amine, (±)-[(5-fluoro-7-pyridin-3-yl-2 ₃ 3-dihydro-l-benzofuran-2-yl)methyl]amine, (-)-[(5-fluoro-7-pyridin-3-yl-2,3-dihydro-l-benzofuran-2-yl) methyl]amine, (+)-{[5-fluoro-7-pyridin-3-yl-2,3-dihydro-l-benzofuran-2-yl] methyl}amine, (±)-[(5-fluoro-7-pyridin-4-yl-2,3-dihydro-l-benzofuran-2-yl )methyl]amine, (±)-[(5-fluoro-7-pyrimidin-5-yl-2,3-dihydro-l-benzofuran-2- yl)methyl]amine,

(±)-{[7-(2,3-dichlorophenyl)-5-fluoro-2,3-dihydro-l-benz ofuran-2-yl]methyl}amine, (±)-{[7-(2,3-dimethoxyphenyl)-5-fluoro-2,3-dihydro-l-benzof uran-2-yl]methyl}amine, (-)-{[7-(2,3-dimethoxyphenyl)-5-fluoro-2,3-dihydro-l-benzofu ran-2-yl]methyl}amine, (+)-{[7-(2,3-dimethoxyphenyl)-5-fluoro-2,3-dihydro-l-benzofu ran-2-yl]methyl}amine, (±)-{[7-(2,4-difluorophenyl)-5-fluoro-2,3-dihydro-l-benzofu ran-2-yl]methyl}amine, (±)-{[7-(2,4-dichlorophenyl)-5-fluoro-2,3-dihydro-l-benzofu ran-2-yl]methyl}amine, (-)-{ [5-fluoro-7-(2,4-dichlorophenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methyl}amine, (+)-{[5-fluoro-7-(2,4-dichlorophenyl)-2,3-dihydro-l-benzofur an-2-yl]methyl}amine, (±)-{[7-(2,4-dimethoxyphenyl)-5-fluoro-2,3-dihydro-l-benzof uran-2-yl]methyl}amine, (±)-{[7-(2,5-difluorophenyl)-5-fluoro-2,3-dihydro-l-benzofu ran-2-yl]methyl}amine, (±)- { [7-(2,5-dichlorophenyl)-5 -fluoro-2,3 -dihydro- 1 -benzofuran-2-yl]methyl } amine, (±)- { [7-(2,5-dimethylphenyl)-5-fluoro-2,3-dihydro- 1 -benzofuran-2-yl] methyl} amine, (±)-{[7-(2,5-dimethoxyphenyl)-5-fluoro-2,3-dihydro-l-benzof uran-2-yl]methyl}amine, (±)-{[5-fluoro-7-(5-methoxy-2-methylphenyl)-2,3-dihydro-l-b enzofuran-2- yl]methyl} amine,

(±)-{[5-fluoro-7-(2-methoxy-5-methylphenyl)-2,3-dihydro- l-benzofuran-2- yl]methyl} amine,

(±)-{[7-(2,6-difluorophenyl)-5-fluoro-2,3-dihydro-l-benz ofuran-2-yl]methyl}amine, (±)- { [7-(2,6-dimethylphenyl)-5-fluoro-2,3-dihydro- 1 -benzofuran-2-yl] methyl} amine, (+)- { [7-(2,6-dimethylphenyl)-5-fluoro-2,3-dihydro- 1 -benzofuran-2-yl]methyl} amine, (-)-{[7-(2,6-dimethylpb.enyl)-5-fluoro-2,3-dihydro-l-benzofu ran-2-yl]methyl}amine, (±)- { [7-(2,6-dichlorophenyl)-5 -fluoro-2,3 -dihydro- 1 -benzofuran-2-yl]methyl} amine, (±)-N-{[7-(2,6-dichlorophenyl)-5-fluoro-2,3-dihydro-l-benzo furan-2- yl] methyl } cyclopropanamine, (±)-l-cyclopropyl-N-{[7-(2,6-dichlorophenyl)-5-fluoro-2,3-d ihydro-l-benzofuran-2- yl] methyl } methanamine, (±)-N-{[7-(2,6-dichlorophenyl)-5-fluoro-2,3-dihydro-l-benzo furan-2- yljmethyl} cyclobutanamine, (±)-N-{[7-(2,6-dichlorophenyl)-5-fluoro-2,3-dihydro-l-benzo furan-2- yl]methyl} ethanamine,

(±)-N-{[7-(2,6-dichlorophenyl)-5-fluoro-2,3-dihydro-l-be nzofuran-2-yl]methyl}propan- 1 -amine,

(±)-N-{[7-(2,6-dichlorophenyl)-5-fluoro-2,3-dihydro-l-be nzofuran-2-yl]methyl}propan-

2-amine, (±)- { [7-(2,6-dichlorophenyl)-5 -fluoro-2,3 -dihydro- 1 -benzofuran-2- yl] methyl } dimethylamine, (±).1 -{ [7-(2,6-dichlorophenyl)-5-fluoro-2,3-dihydro- 1 -benzofuran-2- yl] methyl} piperidine (±)- 1 - { [7-(2,6-dichlorophenyl)-5-fluoro-2,3-dihydro- 1 -benzofuran-2- yl] methyl } morpholine

(±)- 1 - { [7-(2,6-dichlorophenyl)-5-fluoro-2,3-dihydro- 1 -benzofuran-2- yl] methyl} pyrrolidine

(±)- { [5-chloro-7-(2-fluorophenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methyl} amine, (±)- { [5-chloro-7-(2-methoxyphenyl)-2,3-dihydro- 1 -benzofuran-2-yl] methyl} amine, (±)-{[5-chloro-7-(3-furyl)-2,3-dihydro-l-benzofuran-2-yl]me thyl}amine, (±)- { [5-chloro-7-(2,3-difluorophenyl)-2,3-dihydro- 1 -benzofuran-2-yl] methyl} amine, (-)-{[5-chloro-7-(2,3-difluorophenyl)-2,3-dihydro-l-benzofur an-2-yl]methyl}amine, (+)-{[5-chloro-7-(2,3-difluorophenyl)-2,3-dihydro-l-benzofur an-2-yl]methyl}amine, (^)- { [5-chloro-7-(2,3-dichlorophenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methyl} amine,

(±)-{[5-chloro-7-(2,3-dimethylphenyl)-2,3-dihydro-l-benzofu ran-2-yl]methyl}amine, (±)-{[5-chloro-7-(2,3-dimethoxyphenyl)-2,3-dihydro-l-benzof uran-2-yl]methyl}amine ₃ (±)-{[5-chloro-7-(2,4-difluorophenyl)-2,3-dihydro-l-benzofu ran-2-yl]methyl}amine, (±)- { [5-chloro-7-(2,4-dichlorophenyl)-2,3-dihydro- 1 -benzofuran-2-yl] methyl} amine, (-)-{[5-chloro-7-(2,4-dichlorophenyl)-2,3-dihydro-l-benzofur an-2-yl]methyl}amine, (+)-{[5-chloro-7-(2,4-dichlorophenyl)-2,3-dihydro-l-benzofur an-2-yl]methyl}amine, (±)- { [5-chloro-7-(2,4-dimethoxyphenyl)-2,3-dihydro- 1 -benzofuran-2-yl] methyl} amine, (±)-{[5-chloro-7-(2,5-difluorophenyl)-2,3-dihydro-l-benzoft ιran-2-yl]methyl}amine, (±)-{[5-chloro-7-(2,5-dichlorophenyl)-2,3-dihydro-l-benzofu ran-2-yl]methyl}amine, (±)-{[5-chloro-7-(5-chloro-2-methoxyphenyl)-2,3-dihydro-l-b enzofuran-2- yl]methyl} amine,

(±)-{[5-chloro-7-(3,4-difluorophenyl)-2,3-dihydro-l-benz ofuran-2-yl]methyl}amine, (±)- { [5 -chloro-7-(3 -chloro-4-fluorophenyl)-2,3 -dihydro- 1 -benzofuran-2- yl]methyl} amine, (±)- { [5-chloro-7-(2,6-dimethylphenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methyl} amine, (-)- { [5-chloro-7-(2,6-dimethylphenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methyl } amine, (+)- { [5-chloro-7-(2,6-dimethylphenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methyl} amine, (±)~ { [5-chloro-7-(2,6-dichlorophenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methyl} amine, (+)-{[5-chloro-7-(2,6-dichlorophenyl)-2,3-dihydro-l-benzofur an-2-yl]methyl}amine, (-)-{[5-chloro-7-(2,6-dichlorophenyl)-2,3-dihydro-l-benzofur an-2-yl]methyl}amine, (±)-{[(5-chloro-7-pyridin-3-yl-2,3-dihydro-l-benzofuran-2-y l)methyl]amine, (±)-N- { [5-chloro-7-(2,6-dimethylphenyl)-2,3-dihydro- 1 -benzofuran-2- yl] methyl } cyclopropanamine,

(±)-N-{[5-chloro-7-(2,6-dimethylphenyl)-2,3-dihydro-l-be nzofuran-2- yljmethyl} (cyclopropylmethyl)amine,

(±)-N-{[5-chloro-7-(2,6-dimethylphenyl)-2,3-dihydro-l-be nzofuran-2- yljmethyl } cyclobutanamine, (±)-N- { [5-chloro-7-(2,6-dimethylρhenyl)-2,3-dihydro- 1 -benzofuran-2- yl]methyl } ethanamine, (±)-N-{[5-chloro-7-(2,6-dimethylphenyl)-2,3-dihydro-l-benzo furan-2-yl]methyl}propan-

2-amine,

(±)-{[5-chloro-7-(2,6-dimethylphenyl)-2,3-dihydro-l-benz ofuran-2- yl]methyl}dimethylamine, (±)- 1 - { [5-chloro-7-(2,6-dimethylphenyl)-2,3 -dihydro- 1 -benzofuran-2- yl] methyl } piperidine (±)-4-{[5-chloro-7-(2,6-dimethylphenyl)-2,3-dihydro-l-benzo flιran-2- yl] methyl } morpholine (±)-4- { [5-chloro-7-(2,6-dimethylphenyl)-2,3 -dihydro- 1 -benzofuran-2- yl] methyl} thiomorpholine

(±)-N-{[5-chloro-7-(2,6-dimethylphenyl)-2,3-dihydro-l-be nzofuran-2-yl]methyl}propan- 1 -amine,

(±)- 1 - { [5-chloro-7-(2,6-dimethylphenyl)-2,3 -dihydro- 1 -benzofuran-2- yl] methyl } piper azine (±)- 1 - { [5-chloro-7-(2,6-dimethylphenyl)-2,3 -dihydro- 1 -benzofuran-2- yl]methyl}pyrrolidine (±)-{[(5-methyl-7-phenyl-2,3-dihydro-l-benzofuran-2-yl)meth yl]amine,

(±)- { [7-(2-methylphenyl)-5-methyl-2,3-dihydro- 1 -benzofuran-2-yl] methyl} amine, (±)-{[7-(2-fluorophenyl)-5-methyl-2,3-dihydro-l-benzoturan- 2-yl]methyl}amine, (±)-{[7-(2-methoxyplienyl)-5-methyl-2,3-dihydro-l-benzofura n-2-yl]methyl}amine, (±)- { [7-(2-chlorophenyl)-5-methyl-2,3-dihydro- 1 -benzofuran-2~yl]methyl} amine, (±)-({5-methyl-7-[2-(trifluoromethyl)phenyl]-2,3-dihydro-l- benzoturan-2- yl}methyl)amine,

(±)-{[7-(3-chlorophenyl)-5-methyl-2,3-dihydro-l-benzofuran- 2-yl]methyl}amine, (±)-{[7-(3-methylphenyl)-5-methyl-2,3-dihydro-l-benzofuran- 2-yl]methyl}amine, (±)- { [7-(4-methylphenyl)-5-methyl-2,3-dihydro- 1 -benzofuran-2-yl]methyl} amine, (±)-{[7-(4-fluorophenyl)-5-methyl-2,3-dihydro-l-benzoturan- 2-yl]methyl}amine, (±)- { [7-(4-chlorophenyl)-5-methyl-2,3-dihydro- 1 -benzofuran-2-yl]methyl} amine, (-fc)-{[7-(4-methoxyphenyl)-5-methyl-2,3-dihydro-l-benzorura n-2-yl]methyl}amine, (±)-{[7-(2,3-dimethoxyphenyl)-5-methyl-2,3-dihydro-l-benzof uran-2-yl]methyl}amine, (-)-{[ ⁷ -(2,3-dimethoxyphenyl)-5-methyl-2,3-dihydro-l-benzoruran-2-y l]methyl}amine, (+)- { [7-(2,3-dimethoxyphenyl)-5-methyl-2,3-dihydro- 1 -benzofuran-2-yl]methyl} amine, (±)-{[7-(2,4-dichlorophenyl)-5-methyl-2,3-dihydro-l-benzofu ran-2-yl]methyl}amine, (-)- { [7-(2,4-dichlorophenyl)-5-methyl-2,3-dihydro- 1 -benzoturan-2-yl] methyl} amine,

(+)-{[7-(2,4-dichlorophenyl)-5-methyl-2,3-dihydro-l-benzo furan-2-yl]methyl}amine, (±)-{[7-(2,5-dichlorophenyl)-5-methyl-2,3-dihydro-l-benzofu ran-2-yl]methyl}amine, (±)-{[7-(2,6-dimethylphenyl)-5-methyl-2,3-dihydro-l-benzofu ran-2-yl]methyl}amine, (±)- { [7-(2,6-dichlorophenyl)-5-methyl-2,3-dihydro- 1 -benzofuran-2-yl] methyl} amine, (-)- { [7-(2,6-dichlorophenyl)-5-methyl-2,3-dihydro- 1 -benzofuran-2-yl]methyl} amine, (+)- { [7-(2,6-dichlorophenyl)-5-methyl-2,3-dihydro- 1 -benzofuran-2-yl] methyl} amine, (±)- { [5-ethyl-7-(2-methylphenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methyl} amine, (±)- { [5-ethyl-7-(2-chlorophenyl)-2,3-dihydro- 1 -benzofuran-2-yl] methyl} amine, (±)- { [5-isopropyl-7-(2-methylphenyl)-2,3-dihydro- 1 -benzofuran-2-yl] methyl} amine, (±)- { [5-isopropyl-7-(2-chlorophenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methyl} amine, (±)-{[5-cyclopentyl-7-(2-methylphenyl)-2,3-dihydro-l-benzof uran-2-yl]methyl}amine, (±)- { [5-cyclopentyl-7-(2-chlorophenyl)-2,3 -dihydro- 1 -benzofuran-2-yl]methyl } amine, (±)-{[5-isocyano-7-(2-methylphenyl)-2,3-dihydro-l-benzofura n-2-yl]methyl}amine, (±)-{[5-isocyano-7-(2-chlorophenyl)-2,3-dihydro-l-benzofura n-2-yl]methyl}amine, (±)- { [5-(trifluoromethyl)-7-(2-fluorophenyl)-2,3-dihydro- 1 -benzofuran-2- yl] methyl} amine, (±)- { [5-(trifluoromethyl)-7-(2-methylphenyl)-2,3-dihydro- 1 -benzofuran-2- yl]methyl} amine,

(±)- { [5-(trifluoromethyl)-7-(2-chlorophenyl)-2,3-dihydro- 1 -benzofuran-2- yl] methyl} amine,

(±)-{[5-(trifluoromethyl)-7-(2-methoxyphenyl)-2,3-dihydr o-l-benzofuran-2- yl] methyl} amine, (±)- { [5-(trifluoromethyl)-7-(2-(trifluoromethyl)phenyl)-2,3-dihyd ro- 1 -benzofuran-2- yl]methyl} amine, (±)- { [5-(trifluoromethyl)-7-(3-methylphenyl)-2,3-dihydro- 1 -benzofuran-2- yl] methyl } amine, (±)-{[5-(trifluoromethyl)-7-(3-fluorophenyl)-2,3-dihydro-l- benzofuran-2- yl] methyl} amine,

(±)- { [5-(trifluoromethyl)-7-(3-chlorophenyl)-2,3-dihydro- 1 -benzofuran-2- yl] methyl} amine,

(±)-{[5-(trifluoromethyl)-7-(3-methoxyphenyl)-2,3-dihydr o-l-benzofuran-2- yl] methyl} amine,

(±)-{[5-(trifluoromethyl)-7-(3-(trifluoromethyl)phenyl)- 2,3-dihydro-l-benzofuran-2- yl] methyl } amine , (±)-{[5-(trifluoromethyl)-7-(4-methylphenyl)-2,3-dihydro-l- benzofuran-2- yl]methyl} amine, (±)-{[5-(trifluoromethyl)-7-(4-fluorophenyl)-2,3-dihydro-l- benzofuran-2- yl] methyl} amine, (±)-{[5-(trifluoromethyl)-7-(4-chlorophenyl)-2,3-dihydro-l- benzofuran-2- yl]methyl} amine,

(±)-{[5-(trifluoromethyl)-7-(4-methoxyphenyl)-2,3-dihydr o-l-benzofuran-2- yl]methyl} amine,

(±)-{[5-(trifluoromethyl)-7-(4-(trifluoromethyl)phenyl)- 2,3-dihydro-l-benzofuran-2- yl] methyl} amine, (±)-{[7-(2,3-dimethylphenyl)-5-(trifluoromethyl)-2,3-dihydr o-l-benzofuran-2- yl] methyl } amine, (±)-{[7-(2,3-difluorophenyl)-5-(trifluoromethyl)-2,3-dihydr o-l-benzofuran-2- yl]methyl}amine, (±)-{[7-(2,3-dichlorophenyl)-5-(trifluoromethyl)-2,3-dihydr o-l-benzofiiran-2- yl]methyl} amine,

(±)-{[7-(2,3-dimethoxyphenyl)-5-(trifluoromethyl)-2,3-di hydro-l-benzofuran-2- yl] methyl} amine,

(±)-{[7-(2,4-difluorophenyl)-5-(trifluoromethyl)-2,3-dih ydro-l-benzofuran-2- yl]methyl}amine, (±)-{[7-(2,4-dimethoxyphenyl)-5-(trifluoromethyl)-2,3-dihyd ro-l-benzofuran-2- yl]methyl}amine, (±)-{[7-(3,4-difluorophenyl)-5-(trifluoromethyl)-2,3-dihydr o-l-benzofuran-2- yl] methyl} amine, (±)-{[7-(3-chloro-4-fluorophenyl)-5-(trifluoromethyl)-2,3-d ihydro-l-benzofuran-2- yl] methyl} amine,

(±)-{[7-(2,5-difluorophenyl)-5-(trifluoromethyl)-2,3-dih ydro-l-benzofuran-2- yljmethyl} amine,

(±)-{[7-(2,5-dichlorophenyl)-5-(trifluoromethyl)-2,3-dih ydro-l-benzofuran-2- yl]methyl} amine,

(±)-{[7-(2,6-dimethylphenyl)-5-(trifluoromethyl)-2,3-dih ydro-l-benzofuran-2- yl]methyl} amine, (±)- { [7-(4-butylphenyl)-5-(trifluoromethyl)-2,3 -dihydro- 1 -benzofuran-2- yl]methyl}amine, (±)-4-[2-(ammomethyl)-5-(trifluoromethyl)-2,3-dihydro-l-ben zofuran-7-yl]benzonitrile (±)-{[7-(3-furyl)-5-(trifluoromethyl)-2,3-dihydro-l-benzofu ran-2-yl]methyl}amine, (±)-{[7-thien-3-yl-5-(trifluoromethyl)-2,3-dihydro-l-benzof uran-2-yl]methyl}amine, (±)- { [7-pyridin-3-yl-5-(trifluoromethyl)-2,3-dihydro- 1 -benzofuran-2-yl]methyl} amine, (±)-[(5,7-diphenyl-2,3-dihydro-l-benzofuran-2-yl)methyl]ami ne, (=•=)- { [7-(2-chlorophenyl)-5-phenyl-2,3-dihydro- 1 -benzofuran-2-yl]methyl} amine, (±)-{[7-(3-chlorophenyl)-5-phenyl-2,3-dihydro-l-benzofuran- 2-yl]methyl}amine, (±)- { [7-(4-chlorophenyl)-5-phenyl-2,3-dihydro- 1 -benzofuran-2-yl]methyl} amine, (±)- { [7-(2-fluorophenyl)-5-phenyl-2,3-dihydro- 1 -benzofuran-2-yl] methyl} amine, (±)- { [7-(3-fluorophenyl)-5-phenyl-2,3-dihydro- 1 -benzofuran-2-yl]methyl} amine, (±)" { [7-(4-fluorophenyl)-5-phenyl-2,3-dihydro- 1 -benzofuran-2-yl]methyl} amine, (±)-{[7-(2-methylphenyl)-5-phenyl-2,3-dihydro-l-benzoflιra n-2-yl]methyl}amine, (±)-{[7-(3-methylphenyl)-5-phenyl-2,3-dihydro-l-benzofuran- 2-yl]methyl}amine, (±)-{[7-(4-methylphenyl)-5-phenyl-2,3-dihydro-l-benzofuran- 2-yl]methyl}amine, (±)-{[7-(2,4-difluorophenyl)-5-phenyl-2,3-dihydro-l-benzofu ran-2-yl]methyl}amine, (±)-{[7-(2,5-dichlorophenyl)-5-phenyl-2,3-dihydro-l-benzofu ran-2-yl]methyl}amine, (±)- { [7-(2-fluorophenyl)-5-methoxy-2,3-dihydro- 1 -benzofuran-2-yl]methyl} amine, (±)- { [7-(2-chlorophenyl)-5-methoxy-2,3-dihydro- 1 -benzofuran-2-yl]methyl} amine, (±)- { [7-(2-methylphenyl)-5-methoxy-2,3-dihydro- 1 -benzofuran-2-yl]methyl} amine, (±)-{[7-(2-methoxyphenyl)-5-methoxy-2,3-dihydro-l-benzofura n-2-yl]methyl}amine, (±)- { [5-methoxy-7-(3-thienyl)-2,3-dihydro- 1 -benzofuran-2-yl]methyl} amine,

(±)-{[7-(2,3-difluorophenyl)-5-methoxy-2,3-dihydro-l-ben zofuran-2-yl]methyl}amine, (±)- { [7-(2,3-dichlorophenyl)-5-methoxy-2,3-dihydro- 1 -benzofuran-2-yl]methyl} amine, (±)-{[7-(2,3-dimethylphenyl)-5-methoxy-2,3-dihydro-l-benzof uran-2-yl]methyl}amine, (±)- { [7-(2,4-difluorophenyl)-5-methoxy-2,3-dihydro- 1 -benzofuran-2-yl]methyl} amine, (±)-{[7-(2,4-dichlorophenyl)-5-methoxy-2,3-dihydro-l-benzof uran-2-yl]methyl}amine, (±)-{[7-(2,5-difluorophenyl)-5-methoxy-2,3-dihydro-l-benzof uran-2-yl]methyl}amine, (±)- { [7-(2,5-dichlorophenyl)-5-methoxy-2,3-dihydro- 1 -benzofuran-2-yl] methyl} amine,

(+)-{[7-(2,5-dichlorophenyl)-5-methoxy-2,3-dihydro-l-benz ofuran-2-yl]methyl}amine, (-)-{[7-(2,5-dichlorophenyl)-5-methoxy-2,3-dihydro-l-benzofu ran-2-yl]methyl}amine, (±)-{[7-(2,5-dimethylphenyl)-5-methoxy-2,3-dihydro-l-benzof uran-2-yl]methyl}amine, (±)- { [7-(2,5-dimethoxylphenyl)-5-methoxy-2,3-dihydro- 1 -benzofuran-2- yl]methyl} amine,

(±)- { [7-(5-chloro-2-methoxyphenyl)-5-methoxy-2,3-dihydro- 1 -benzofuran-2- y 1] methyl } amine,

(±)-{[7-(3-chloro-4-fluorophenyl)-5-methoxy-2,3-dihydro- l-benzofuran-2- yl]methyl}amine, (±)- { [7-(2,6-dimethylphenyl)-5-methoxy-2,3-dihydro- 1 -benzofuran-2-yl]methyl} amine, (±)- { [7-fluoro-5-(2-methylphenyl)-2,3-dihydro- 1 -benzofuran-2-yl] methyl} amine, (±)-{[7-fluoro-5-(2-chlorophenyl)-2,3-dihydro-l-benzoftιra n-2-yl]methyl}amine, (±)- { [7-fluoro-5-(2-fluorophenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methyl} amine, (±)-({7-fluoro-5-[2-(trifluoromethyl)phenyl]-2,3-dihydro-l- benzofuran-2- yl}methyl)amine,

(±)-{[7-fluoro-5-(2-methoxyphenyl)-2,3-dihydro-l-benzofu ran-2-yl]methyl}amine, (±)- { [7-fluoro-5-(3-methylphenyl)-2,3-dihydro- 1 -benzofuran-2-yl] methyl} amine, (±)- { [7-fluoro-5-(3-fluorophenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methyl} amine, (±)- { [7-fluoro-5-(3-chlorophenyl)-2,3-dihydro- 1 -benzofuran-2-yl] methyl} amine, (±)-({7-fluoro-5-[3-(trifluoromethyl)phenyl]-2,3-dihydro-l- benzofuran-2- yl}methyl)amine,

(±)-{[7-fluoro-5-(3-methoxyphenyl)-2,3-dihydro-l-benzofu ran-2-yl]methyl}amine, (±)-{[7-fluoro-5-(4-methylphenyl)-2,3-dihydro-l-benzofuran- 2-yl]methyl}amine, (±)-{[7-fluoro-5-(4-chlorophenyl)-2,3-dihydro-l-benzofuran- 2-yl]methyl}amine, (±)- { [7-fluoro-5-(4-fluorophenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methyl} amine, (±)-({7-fluoro-5-[4-(trifluoromethyl)phenyl]-2,3-dihydro-l- benzofuran-2- yl}methyl)amine,

(±)- { [7-fluoro-5-(4-methoxyphenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methyl} amine, (±)-N- { [7-(2,6-dichlorophenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methyl} ethanamine, (±)-N-{[7-(2,6-dichlorophenyl)-2,3-dihydro-l-benzofuran-2- yl] methyl } cyclopropanamine, (±)-N-{[7-(2,6-dichlorophenyl)-2,3-dihydro-l-benzofuran-2-y l]methyl}cyclobutanamine,

(±)-N-{[7-(2,6-dichlorophenyl)-2,3-dihydro-l-benzofuran-2-y l]methyl}propan-2-amine, (±)-{[6-fluoro-7-(2-methylphenyl)-2,3-dihydro-l-benzofuran- 2-yl]methyl}amine, (+)-{[6-fluoro-7-(2-methylphenyl)-2,3-dihydro-l-benzofuran-2 -yl]methyl}amine, (-)- { [6-fluoro-7-(2-methylphenyl)-2,3 -dihydro- 1 -benzofuran-2-yl]methyl} amine, (±)- { [ { [7-(2-chlorophenyl)-6-fluoro-2,3 -dihydro- 1 -benzofuran-2-yl]methyl } amine, (±)- { [6-chloro-7-(2-methylphenyl)-2,3 -dihydro- 1 -benzofuran-2~yl]methyl } amine, (±)-{[6-chloro-7-(2-chlorophenyl)-2,3-dihydro-l-benzoruran- 2-yl]methyl}amine, (±)-{[6-fluoro-7-(2-methylphenyl)-2,3-dihydro-l-benzoruran- 2-yl]methyl}methylamine, (±)-{[6-fluoro-7-(2-chlorophenyl)-2,3-dihydro-l-benzoturan- 2-yl]methyl}methylamine, (±)-{ [6-chloro-7-(2-methylphenyl)-2,3-dihydro-l -benzofuran-2-yl]methyl}methylamine, (±)-{[6-chloro-7-(2-chlorophenyl)-2,3-dihydro-l-benzofuran- 2-yl]methyl}methylamine, (±)-[(N-methyl-l-[7-(2-methylphenyl)-2,3-dihydro-l-benzofur an-2-yl]methanamine, (-)-N-methyl-l-[7-(2-methylphenyl)-2,3-dihydro-l-benzofuran- 2-yl]methanamine, (+)-N-methyl-l-[7-(2-methylphenyl)-2,3-dihydro-l-benzofuran- 2-yl]methanamine, (±)-[(N-methyl- 1 -[7-(2-chlorophenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methanamine, (+)-N-methyl-l-[7-(2-chlorophenyl)-2 ₃ 3-dihydro-l-benzoturan-2-yl]methanamine, (-)-N-methyl-l-[7-(2-chlorophenyl)-2,3-dihydro-l-benzoturan- 2-yl]methanamine, (±)-[(N-methyl-l-[7-(2-fluorophenyl)-2,3-dihydro-l-benzofur an-2-yl]methanamine, (±)-[(N-methyl-l-[7-(2-methoxyphenyl)-2,3-dihydro-l-benzofl ιran-2-yl]methanamine, (±)-[(N-methyl-l-[7-(3-methylphenyl)-2,3-dihydro-l-benzorur an-2-yl]methanamine, (±)-[(N-methyl-l-[7-(3-fluorophenyl)-2,3-dihydro-l-benzofur an-2-yl]methanamine, (±)-[(N-methyl-l-[7-(3-chlorophenyl)-2,3-dihydro-l-benzorur an-2-yl]methanamine, (±)-[(N-methyl- 1 - [7-(3 -methoxyphenyl)-2,3 -dihydro- 1 -benzofuran-2-yl]methanamine, (±)-[(N-methyl-l-[7-(4-methylphenyl)-2,3-dihydro-l-benzofur an-2-yl]methanamine, (±)-[(N-methyl- 1 -[7-(4-fluorophenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methanamine, (±)-[(N-methyl-l-[7-(4-chlorophenyl)-2,3-dihydro-l-benzorur an-2-yl]methanamine, (±)- [(N-methyl- 1 - [7-(4-methoxyphenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methanamine, (±)-[(N-methyl-l-[7-(2,3-dimethylphenyl)-2,3-dihydro-l-benz ofuran-2-yl]methanamine, (±)-[(N-methyl-l-[7-(2,3-dimethoxyphenyl)-2,3-dihydro-l-ben zofuran-2- yljmethanamine,

(±)-[(N-methyl-l-[7-(2,4-difluorophenyl)-2,3-dihydro-l-b enzofuran-2-yl]methanamine, (±)-[(N-methyl-l-[7-(2,4-dichlorophenyl)-2,3-dihydro-l-benz ofuran-2-yl]methanamine,

(±)-[(N-methyl- 1 -[7-(2,4-dimethoxyphenyl)-2,3-dihydro- 1 -benzofuran-2- yl]methanamine,

(±)-[(N-methyl-l-[7-(2,5-dimethylphenyl)-2,3-dihydro-l-b enzofuran-2-yl]methanamine, (±)-[(N-methyl- 1 -[7-(2,5-difluorophenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methanamine, (±)-[(N-methyl-l-[7-(2,5-dichlorophenyl)-2,3-dihydro-l-benz ofuran-2-yl]methanamine, (±)-[(N-methyl-l-[7-(5-chloro-2-methoxyphenyl)-2,3-dihydro- l-benzofuran-2- yljmethanamine, (±)-[(N-methyl-l-[7-(5-chloro-2-methylρhenyl)-2,3-dihydro- l-benzofuran-2- yljmethanamine, (±)-[(N-methyl- 1 -[7-(2,6-dimethylphenyl)-2,3-dihydro- 1 ~benzofiiran-2-yl]methanamine, (±)-[(N-methyl-l-[7-(2,6-dichlorophenyl)-2,3-dihydro-l-benz oflιran-2-yl]methanamine, (-)-{[7-(2,6-dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]m ethyl}methylamine, (+)-{[7-(2,6-dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]m ethyl}methylamine, (±)-N-methyl- 1 -(7-pyridin-3-yl-2,3-dihydro- 1 -benzofuran-2-yl)methanamine, (±)-[(N-methyl-l-[7-(2,3-difluorophenyl)-2,3-dihydro-l-benz ofuran-2-yl]methanamine, (±)-{[5-fluoro-7-(2-fluorophenyl)-2,3-dihydro-l-benzofuran- 2-yl]methyl}methylamine, (±)- { [5-fluoro-7-(2-chlorophenyl)-2,3-dihydro- 1 -benzofuran-2-yl] methyl } methylamine, (±)-{[5-fluoro-7-(2-methylphenyl)-2,3-dihydro-l-benzofuran- 2-yl]methyl}methylamine, (-)-{[5-fluoro-7-(2-methylphenyl)-2,3-dihydro-l-benzofuran-2 -yl]methyl}methylamine, (+)-{[5-fluoro-7-(2-methylphenyl)-2,3-dihydro-l-benzofuran-2 -yl]methyl}methylamine, (±)- { [5-fluoro-7-(2-methoxyphenyl)-2,3-dihydro- 1 -benzofuran-2- yl] methyl } methylamine, (±)-{[7-(2,3-dimethoxyphenyl)-5-fluoro-2,3-dihydro-l-benzof uran-2- yl]methyl}methylamine, (±)-[7-(2,4-dichlorophenyl)-5-fluoro-2,3-dihydro- 1 -benzofuran-2- yl] methyl } methylamine,

(-)-[7-(2,4-dichlorophenyl)-5-fluoro-2,3-dihydro-l-benzof uran-2-yl]methyl}methylamine, (+)- [7-(2,4-dichlorophenyl)-5-fluoro-2,3 -dihydro- 1 -benzofuran-2- yl]methyl}methylamine, (±)-{[7-(2,5-difluorophenyl)-5-fluoro-2,3-dihydro-l-benzofu ran-2- yl]methyl}methylamine,

(±)- { [7-(2,5-dichlorophenyl)-5 -fluoro-2,3 -dihydro- 1 -benzofuran-2- yl]methyl}methylamine, (+)-{[5-fluoro-7-(2,5-dichlorophenyl)-2,3-dihydro-l-benzofur an-2- yl]methyl}methylamine, (-)-{[5-fluoro-7-(2,5-dichlorophenyl)-2,3-dihydro-l-benzofur an-2- yl] methyl } methylamine, (±)-{[7-(2,5-dimethylphenyl)-5-fluoro-2,3-dihydro-l-benzofl ιran-2- yl] methyl } methylamine,

(±)- { [7-(2,6-dimethylphenyl)-5 -fluoro-2,3 -dihydro- 1 -benzofuran-2- yl]methyl}methylamine,

(±)-{[7-(2,6-dichlorophenyl)-5-fluoro-2,3-dihydro-l-benz ofuran-2- yl]methyl}methylamine, (±)-{[5-fluoro-7-(5-methoxy-2-methylphenyl)-2,3-dihydro-l-b enzofuran-2- yl] methyl } methylamine, (±)-{[5-fluoro-7-(2-methoxy-5-methylphenyl)-2,3-dihydro-l-b enzofuran-2- yl] methyl } methylamine, (±)-{[7-(5-chloro-2-methoxyphenyl)-5-fluoro-2,3-dihydro-l-b enzofuran-2- yl] methyl } methylamine,

(±)-[(5-fluoro-7-pyridin-3-yl-2,3-dihydro-l-benzofuran-2 -yl)methyl]methylamine, (±)-[(5-chloro-7-(2-methoxyphenyl)-2,3-dihydro- 1 -benzofuran-2- yl] methyl } methylamine, (±)-{[5-chloro-7-(2,6-dimethylphenyl)-2,3-dihydro-l-benzofu ran-2- yl] methyl } methylamine,

(±)-[(5-chloro-7-(2-fluorophenyl)-2,3-dihydro-l-benzofur an-2-yl]methyl}methylamine, (±)-{[5-chloro-7-(2,3-difluorophenyl)-2,3-dihydro-l-benzofu ran-2- yl] methyl } methylamine, (±)-{[5-chloro-7-(2,3-dichloroρhenyl)-2,3-dihydro-l-benzof uran-2- yl]methyl}methylamine,

(±)-{[5-chloro-7-(2,3-dimethylρhenyl)-2,3-dihydro-l-ben zofuran-2- yl]methyl}methylamine,

(±)-{ [5-chloro-7-(2 ₅ 3-dimethoxyphenyl)-2,3-dihydro- 1 -benzofuran-2- yl]methyl}methylamine,

(±)-{[5-chloro-7-(2,4-difluorophenyl)-2,3-dihydro-l-benz ofuran-2- yl]methyl}methylamine, (±)-{[5-chloro-7-(2,4-dichlorophenyl)-2,3-dihydro-l-benzofu ran-2- yl]methyl}methylamine, (±)- { [5-chloro-7-(2,4-dimethoxyphenyl)-2,3-dihydro- 1 -benzofuran-2- yl]methyl } methylamine, (±)- { [5-chloro-7-(2,5-difluorophenyl)-2,3-dihydro- 1 -benzofuran-2- yljmethyl } methylamine,

(±)-{[5-chloro-7-(2,5-dichlorophenyl)-2,3-dihydro-l-benz ofuran-2- yl] methyl } methylamine,

(±)-{[5-chloro-7-(5-chloro-2-methoxyphenyl)-2,3-dihydro- l-benzofuran-2- yl] methyl } methylamine, (±)- { [5-chloro-7-(3.4-difluorophenyl)-2,3-dihydro- 1 -benzofuran-2- yl] methyl } methylamine, (±)-[5-chloro-7-(3-chloro-4-fluorophenyl)-2,3-dihydro-l-ben zoftιran-2- yl] methyl } methylamine,

(±)-{[7-(2-fluorophenyl)-5-methyl-2,3-dihydro-l-benzofur an-2-yl]methyl}methylamine, (±)-{[7-(2-chlorophenyl)-5-methyl-2,3-dihydro-l-benzofuran- 2-yl]methyl}methylamine, (±)-{[7-(2-methoxyphenyl)-5-methyl-2,3-dihydro-l-benzofuran -2- yl]methyl}methylamine,

(±)-{[7-(3-methylphenyl)-5-methyl-2,3-dihydro-l-benzofur an-2-yl]methyl}methylamine, (±)-{[7-(3-chlorophenyl)-5-methyl-2,3-dihydro-l-benzofuran- 2-yl]methyl}methylamine, (±)-{[7-(4-methylphenyl)-5-methyl-2,3-dihydro-l-benzofuran- 2-yl]methyl}methylamine, (±)-{[7-(4-chlorophenyl)-5-methyl-2,3-dihydro-l-benzofuran- 2-yl]methyl}methylamine, (±)-{[7-(4-fluorophenyl)-5-methyl-2,3-dihydro-l-benzofuran- 2-yl]methyl}methylamine, (±)- { [7-(4-methoxyphenyl)-5 -methyl -2,3 -dihydro- 1 -benzofuran-2- yl] methyl } methylamine, (±)- { [7-(2,3 -dimethoxyphenyl)-5-methyl-2,3 -dihydro- 1 -benzofuran-2- yl]methyl}methylamine, (±)-{ [7-(2,4-dichlorophenyl)-5-methyl-2,3-dihydro-l -benzofuran-2- yl]methyl}methylamine,

(±)-{[7-(2,5-dichlorophenyl)-5-methyl-2 ₅ 3-dihydro-l-benzofuran-2- yl] methyl } methylamine, (+)-{[7-(2,5-dichloroρhenyl)-5-methyl-2,3-dihydro-l-benzofu ran-2- yl] methyl } methylamine, (-)-{[7-(2,5-dichlorophenyl)-5-methyl-2,3-dihydro-l-benzofur an-2- yl] methyl } methylamine, (±)-{[7-(2,6-dimethylphenyl)-5-methyl-2,3-dihydro-l-benzofu ran-2- yl] methyl } methylamine,

(±)- { [7-(2,6-dichlorophenyl)-5-methyl-2,3-dihydro- 1 -benzoflιran-2- yl]methyl}methylamine,

(±)-{[7-(2-fluorophenyl)-5-methoxy-2,3-dihydro-l-benzofu ran-2- yl] methyl } methylamine, (±)- { [7-(2-chlorophenyl)-5-methoxy-2,3 -dihydro- 1 -benzofuran-2- yl] methyl } methylamine, (±)" { [7-(2-methylphenyl)-5-methoxy-2,3-dihydro- 1 -benzofuran-2- yl] methyl } methylamine, (±)-{[7-(2,3-difluorophenyl)-5-methoxy-2,3-dihydro-l-benzof tiran-2- yl] methyl } methylamine,

(±)- { [7-(2,3-dichlorophenyl)-5-methoxy-2,3-dihydro- 1 -benzofϊιran-2- yl]methyl}methylamine,

(±)-{[7-(2,3-dimethylphenyl)-5-methoxy-2,3-dihydro-l-ben zofuran-2- yl] methyl } methylamine, (±)-{[7-(2,4-difluorophenyl)-5-methoxy-2,3-dihydro-l-benzof uran-2- yl] methyl } methylamine, (±)- { [7-(2,5-difluorophenyl)-5-methoxy-2,3-dihydro- 1 -benzofuran-2- yl] methyl } methylamine, (±)-{[7-(2,5-dichlorophenyl)-5-methoxy-2,3-dihydro-l-benzof iiran-2- yl]methyl } methylamine,

(±)-{[7-(2,5-dimethylphenyl)-5-methoxy-2,3-dihydro-l-ben zofuran-2- yl]methyl}methylamine,

(±)-{[7-(2,5-dimethoxyphenyl)-5-methoxy-2,3-dihydro-l-be nzofuran-2- yl]methyl } methylamine,

(±)- { [7-(5-chloro-2-methoxyphenyl)-5-methoxy-2,3-dihydro- 1 -benzofuran-2- yl]methyl}methylamine, (±)-{[7-(3-chloro-4-fluorophenyl)-5-methoxy-2,3-dihydro-l-b enzofLiran-2- yl]methyl}methylamine, (±)-{ [7-(2 ₅ 6-dimethylphenyl)-5-methoxy-2,3-dihydro-l -benzofuran-2- yl]methyl}methylamine,

(±)-{[7-(2-chlorophenyl)-5-phenyl-2,3-dihydro-l-benzofur an-2-yl]methyl}methylamine, (±)-{[7-(3-chlorophenyl)-5-phenyl-2,3-dihydro-l-benzofuran- 2-yl]methyl}methylamine, (±)-{[7-(4-chlorophenyl)-5-phenyl-2,3-dihydro-l-benzofuran- 2-yl]methyl}methylamine, (±)-{[7-(2-fluorophenyl)-5-phenyl-2,3-dihydro-l-benzofuran- 2-yl]methyl}methylamine, (±)-{[7-(3-fluoropb.enyl)-5-phenyl-2,3-dihydro-l-benzofuran -2-yl]methyl}methylamme, (±)-{[7-(4-fluorophenyl)-5-phenyl-2,3-dihydro-l-benzofuran- 2-yl]methyl}niethylamine, (±)-{[7-(2-methylphenyl)-5-phenyl-2,3-dihydro-l-benzofuran- 2-yl]methyl}methylamine, (±)-{[7-(3-methylphenyl)-5-phenyl-2,3-dihydro-l-benzofuran- 2-yl]methyl}methylamine, (±)-{[7-(4-methylphenyl)-5-phenyl-2,3-dihydro-l-benzofuran- 2-yl]methyl}methylamine, (±)- { [7-(2-methoxyphenyl)-5-phenyl-2,3 -dihydro- 1 -benzofuran-2- yl] methyl } methylamine, (±)-{[7-(3-methoxyphenyl)-5-phenyl-2,3-dihydro-l-benzofuran -2- yl] methyl } methylamine, (±)- { [7-(4-methoxyphenyl)-5 -phenyl-2,3 -dihydro- 1 -benzofuran-2- y 1] methyl } methylamine , (±)- { [7-(2,4-difluorophenyl)-5-phenyl-2,3 -dihydro- 1 -benzofuran-2- yl] methyl } methylamine,

(±)-{[N-methyl-l-[7-phenyl-5-(trifluoromethyl)-2,3-dihyd ro-l-benzofuran-2- yljmethanamine,

(±)-N-methyl-l-[7-(3-methylphenyl)-5-(trifluoromethyl)-2 ,3-dihydro-l-benzofuran-2- yljmethanamine, (±)-N-methyl-l-[7-(3-fluorophenyl)-5-(trifluoromethyl)-2,3- dihydro-l-benzofuran-2- yljmethanamine, (±)-N-methyl-l-[7-(2,3-difluorophenyl)-5-(trifluoromethyl)- 2,3-dihydro-l-benzofuran-2- yl]methanamine,

(±)-N-methyl-l-[7-(3,4-difluorophenyl)-5-(trifluoromethy l)-2,3-dihydro-l-benzofuran-2- yl]methanamine, (±)-N-methyl-l-[7-(2,5-difluorophenyl)-5-(trifluoromethyl)- 2,3-dihydro-l-benzofuran-2- yl] methanamine, (±)-N-methyl-l-[7-(2,3-dichlorophenyl)-5-(trifluoromethyl)- 2,3-dihydro-l-benzofuran-2- yl] methanamine, (±)-{[7-(3-chloro-4-fluorophenyl)-5-(trifluoromethyl)-2,3-d ihydro-l-benzofuran-2- yl]methyl}methylamine,

(±)-N-methyl- 1 - [7-(2,4-dimethoxyphenyl)-5 -(trifluoromethyl)-2,3-dihydro- 1 -benzofuran- 2-yl] methanamine,

(±)-{[7-[3,5-bis(trifluoromethyl)phenyl]-5-(trifluoromet hyl)-2,3-dihydro-l-benzofuran-2- yl] methyl } methylamine,

(±)-{[7-fluoro-5-(2-methylphenyl)-2,3-dihydro-l-benzofur an-2-yl]methyl}methylamine, (±)-{[7-fluoro-5-(2-chlorophenyl)-2,3-dihydro-l-benzofuran- 2-yl]methyl}methylamine, (±)-{[7-fluoro-5-(2-fluorophenyl)-2,3-dihydro-l-benzofuran- 2-yl]methyl}methylamine, (±)-{7-fluoro-5-[2-(trifluoromethyl)phenyl]-2,3-dihydro-l-b enzofuran-2- yl } methyl)methylamine,

(±)- { 7-fluoro-5 - [2-niethoxyphenyl] -2,3 -dihydro- 1 -benzofuran-2-yl }methyl)methylamine, (±)- { 7-fluoro-5 - [3 -methylphenyl] -2,3 -dihydro- 1 -benzofuran-2-yl}methyl)methylamine, (±)-{7-fluoro-5-[3-chlorophenyl]-2,3-dihydro-l-benzofuran-2 -yl}methyl)methylamine, (±)-{[7-fluoro-5-(3-fluorophenyl)-2,3-dihydro-l-benzofuran- 2-yl]methyl}methylamine, (±)- { 7-fluoro-5 - [3-(trifluoromethyl)phenyl] -2,3-dihydro- 1 -benzofuran-2- yl}methyl)methylamine,

(±)-{7-fluoro-5-[3-methoxyphenyl]-2,3-dihydro-l-benzofur an-2-yl}methyl)methylamine, (±)-{7-fluoro-5-[4-methylphenyl]-2,3-dihydro-l-benzofuran-2 -yl}methyl)methylamine, (±)- { 7-fluoro-5 - [4-chlorophenyl] -2,3-dihydro- 1 -benzoruran-2-yl}methyl)methylamine, (±)- { [7-fluoro-5-(4-fluorophenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methyl} methylamine, (±)-{7-fluoro-5-[4-(trifluoromethyl)phenyl]-2,3-dihydro-l-b enzoruran-2- yl } methyl)methylamine, (±)-{7-fluoro-5-[4-methoxyphenyl]-2,3-dihydro-l-benzofuran- 2-yl}methyl)methylamine, (+){[7-(2,6-dichlorophenyl)-5-fluoro-2,3-dihydro-l-benzofura n-2- yl]methyl}methylamine,

(-) { [7-(2,6-dichlorophenyl)-5-fluoro-2,3 -dihydro- 1 -benzofuran-2- yl]methyl}methylamine,

(R)-[7-(2-chloro-phenyl)-(5-Fluoro-2,3-dihydro-benzofuran -2-ylmethyl)methyl-amine, (R)-[7-(2,6-dichloro-phenyl)-5-Fluoro-2,3-dihydro-benzofuran -2-ylmethyl]ethylamine, (R)-[7-(2,6-dichloro-phenyl)-5-Fluoro-2,3-dihydro-benzoftιr an-2- ylmethyl] dimethylamine, { [(2R)-7-(5-chloro-2-methylphenyl)-5-fluoro-2,3-dihydro- 1 -benzofuran-2- yl] methyl } amine,

{ [(2R)-7-(4-chloro-2-methylρhenyl)-5-fluoro-2,3-dihydro- 1 -benzofaran-2- yl] methyl } amine,

(-)- { [7-(2,6-dichlorophenyl)-5-fluoro-2,3-dihydro- 1 -benzofuran-2-yl]methyl} amine, (+)-{[7-(2,6 dichlorophenyl)-5-fluoro-2,3-dihydro-l-benzofuran-2-yl]methy l}amine, (±)-{2-[6-chloro-7-(2-chlorophenyl)-2,3-dihydro-l-benzofura n-2-yl]ethyl}amine, (±)-{2-[7-(2,6-dichlorophenyl)-5-fluoro-2,3-dihydro-l-benzo furan-2-yl]ethyl}amine, (±)-{2-[7-(2-methoxyphenyl)-5-methoxy-2,3-dihydro-l-benzofi αran-2-yl]ethyl}amine, (±)- {N-methyl- 1 - [(7-(2,4,6~trichlorophenyl)-2,3 -dihydro- 1 -benzofuran-2- yl]methanamine, (+)- {N-methyl- 1 - [(7-(2,4,6-trichlorophenyl)-2,3 -dihydro- 1 -benzofuran-2- yljmethanamine, (-)- {N-methyl- 1 -[(7-(2,4,6-trichlorophenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methanamine, (+)-{ [7-(2,6-dimethylphenyl)-5 -fluoro-2,3 -dihydro- 1 -benzofαran-2- yl] methyl } methylamine, (-)-{[7-(2,6-dimethylphenyl)-5-fluoro-2,3-dihydro-l-benzorur an-2- yl] methyl } methylamine, (-)-{[7-(2,6-dimethylphenyl)-5-methoxy-2,3-dihydro-l-benzofu ran-2- yl]methyl}methylamine, (+)-{[7-(2,6-dimethylphenyl)-5-methoxy-2,3-dihydro-l-benzofu ran-2- yl]methyl } methylamine,

(+)- { [5-chloro-7-(2,5-dichlorophenyl)-2,3-dihydro- 1 -benzoforan-2- yl] methyl} methylamine,

(-)-{[5-chloro-7-(2,5-dichlorophenyl)-2,3-dihydro-l-benzo furan-2- yl] methyl } methylamine,

(-)-{[5-chloro-7-(2,6-dimethylphenyl)-2,3-dihydro-l-benzo furan-2- yl]methyl}methylamine, (+)-{[5-chloro-7-(2,6-dimethylphenyl)-2,3-dihydro-l-benzofur an-2- yl]methyl}methylamine, (+)-{ [7-(2,3-dimethoxyphenyl)-5-methyl-2,3-dihydro-l -benzofuran-2- yljmethyl } methylamine, (-)-{[7-(2,3-dimethoxyphenyl)-5-methyl-2,3-dihydro-l-benzofu ran-2- yl]methyl}methylamine,

(-)- { [7-(2,3-dimethoxyphenyl)-5-fluoro-2,3-dihydro- 1 -benzofuran-2- yl] methyl } methylamine, or

(+)-{[7-(2,3-dimethoxyphenyl)-5-fluoro-2,3-dihydro-l-benz ofuran-2- yl]methyl } methylamine ; or a pharmaceutically acceptable salt thereof.

As one skilled in the art will recognize the optical rotation of an enantiomer can change depending on its form (e.g. free base versus salt form). Moreover one skilled in the art will recognize that one of the enantiomers selected from (+) and (-) has an absolute configuration of (R), where as the other has an absolute configuration of (S). In certain embodiments of the invention, compounds above having an absolute (R) configuration are preferred. The compounds of Formula 1 have affinity for and agonist or partial agonist activity at the 2c subtype of brain serotonin receptors and are thus of interest for the treatment of mental disorders, including psychotic disorders such as schizophrenia including paranoid type, disorganized type, catatonic type, and undifferentiated type, schizophreniform disorder, schizoaffective disorder, delusional disorder, substance- induced psychotic disorder, and psychotic disorder not otherwise specified; L-DOPA- induced psychosis; psychosis associated with Alzheimer's dementia; psychosis associated with Parkinson's disease; psychosis associated with Lewy body disease; bipolar disorders such as bipolar I disorder, bipolar II disorder, and cyclothymic disorder; depressive disorders such as major depressive disorder, dysthymic disorder, substance-induced mood disorder, and depressive disorder not otherwise specified; mood episodes such as major depressive episode, manic episode, mixed episode, and hypomanic episode; anxiety disorders such as panic attack, agoraphobia, panic disorder, specific phobia, social

phobia, obsessive compulsive disorder, posttraumatic stress disorder, acute stress disorder, generalized anxiety disorder, separation anxiety disorder, substance-induced anxiety disorder, and anxiety disorder not otherwise specified; adjustment disorders such as adjustment disorders with anxiety and/or depressed mood; intellectual deficit disorders such as dementia, Alzheimer's disease, and memory deficit; eating disorders (e.g., hyperphagia, bulimia or anorexia nervosa) and combinations of these mental disorders that may be present in a mammal. For example, mood disorders such as depressive disorders or bipolar disorders often accompany psychotic disorders such as schizophrenia. A more complete description of the aforementioned mental disorders can be found in the Diagnostic and Statistical Manual of Mental Disorders, 4 ^th edition, Washington, DC,

American Psychiatric Association (1994), incorporated herein by reference in its entirety.

The compounds of formula 1 are also of interest for the treatment of epilepsy; migraines; sexual dysfunction; sleep disorders; substance abuse, including addiction to alcohol and various drugs, including cocaine and nicotine; gastrointestinal disorders, such as malfunction of gastrointestinal motility; and obesity, with its consequent comorbidities including Type II diabetes, cardiovascular disease, hypertension, hyperlipidemia, stroke, osteoarthritis, sleep apnea, gall bladder disease, gout, some cancers, some infertility, and early mortality.

The compounds of Formula 1 can also be used to treat central nervous system deficiencies associated, for example, with trauma, stroke, and spinal cord injuries. The compounds of Formula 1 can therefore be used to improve or inhibit further degradation of central nervous system activity during or following the malady or trauma in question. Included in these improvements are maintenance or improvement in motor and motility skills, control, coordination and strength. In certain embodiments, the present invention therefore provides methods of treating, each of the conditions listed above in a patient, preferably in a human, the methods including administering a therapeutically effective amount of at least one compound of Formula 1 or a pharmaceutically acceptable salt thereof to a patient suffering from such a condition. In other embodiments, the invention relates to compositions comprising at least one compound of Formula 1, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers, excipients, or diluents. Such compositions

include pharmaceutical compositions for treating or controlling disease states or conditions of the central nervous system. In certain embodiments, the compositions comprise mixtures of one or more compounds of Formula 1.

Certain of the compounds of Formula 1 contain stereogenic carbon atoms or other chiral elements (i.e. chirality axis) and thus give rise to stereoisomers, including enantiomers, diastereomers, and in the case of biphenyls, the formation of atropisomers. For definitions and an extensive discourse on atropisomers, see: Eliel, E.L. Stereochemistry of Organic Compounds (John Wiley & Sons, 1994, p 1142), which is incorporated herein by reference in its entirety. Although the stereochemistry is not shown in Formula 1, Formula 1 includes all of the stereoisomers of the l-(2,3-dihydro-l- benzofuran-2-yl)alkanamine derivatives, as well as mixtures of the stereoisomers. Throughout this application, the name of the product, where the absolute configuration of an asymmetric center is not indicated, is intended to embrace the individual stereoisomers as well as mixtures of stereoisomers. When it is necessary to distinguish the enantiomers from one another and from the racemate, the sign of the optical rotation [(+), (-) and (±)] is utilized. Furthermore, throughout this application, the designations R* and S* are used to indicate relative stereochemistry, employing the Chemical Abstracts convention which automatically assigns R* to the lowest numbered asymmetric center.

Where a stereoisomer is preferred, it may, in some embodiments, be provided substantially free of the corresponding stereoisomer. Thus, a stereoisomer substantially free of the corresponding stereoisomer refers to a compound that is isolated or separated via separation techniques or prepared free of the corresponding stereoisomer. "Substantially free," as used herein, means that the compound is made up of a significantly greater proportion of one stereoisomer. In preferred embodiments, the compound is made up of at least about 90% by weight of a preferred stereoisomer. In other embodiments of the invention, the compound is made up of at least about 99% by weight of a preferred stereoisomer. Preferred stereoisomers can be isolated from racemic mixtures by any method known to those skilled in the art, including high performance liquid chromatography (HPLC) and the formation and crystallization of chiral salts, or preferred stereoisomers can be prepared by methods described herein. Methods for the preparation of preferred stereoisomers are described, for example, in Jacques, et al., Enantiomers, Racemates and Resolutions (Wiley Interscience, New York, 1981); Wilen,

S.H., et al., Tetrahedron 33:2725 (1977); Eliel, E.L. Stereochemistry of Carbon Compounds (McGraw-Hill, NY, 1962); and Wilen, S. H. Tables of Resolving Agents and Optical Resolutions p. 268 (E.L. Eliel, Ed., Univ. of Notre Dame Press, Notre Dame, IN 1972), each of which is hereby incorporated by reference in its entirety.

This invention alsoprovides processes for preparing compounds of formula I which processes include one of the following:

a) reacting a compound of formula 7

wherein R ¹ , R ² , R ³ , R ⁴ , R ⁵ , R ⁶ ,and R ⁷ are as defined herein, with sodium azide and reducing the product to give a compound of formula 1 wherein n is 1 and R and R' are both H; or

b) reacting a compound of formula 7 as defined above with an amine of formula NHRR' where R and R' are as defined herein to give a corresponding compound of formula 1 wherein n is 1 ; or

c) reacting a compound of formula 7 as defined above with sodium cyanide followed by reduction to give a compound of formula 1 wherein n is 2 and R and R' are both H;

d) converting a compound of formula 1 as defined herein to a pharmaceutically acceptable salt or vice versa;

or e) isolating a specific enantiomer or diastereomer of a compound of formula 1 or a pharmaceutically acceptable salt thereof as defined herein from a mixture thereof.

The l-(2,3-dihydro-l-benzofuran-2-yl)alkanamine derivatives of Formula 1 may be prepared as illustrated in Scheme I.

Scheme I

Proc A 1 a) NaN3, DMSO and b) reduction, or 2 NHRRVDMSO Proc B 1 a) NaCN/DMSO and b) H ₂ /5% Rh on Al ₂ O ₃ , NH ₄ OH

Variables used are as defined for Formula 1, unless otherwise noted. The appropriately substituted phenol (2) is alkylated with an appropriately substituted allyl bromide or alcohol (3) in the presence of a suitable base such as potassium carbonate in a solvent such as iV,N-dimethylformamide. The phenols, allyl bromides, and allyl alcohols appropriate for the synthesis of the compounds of formula I are either known compounds

or can readily be prepared by one skilled in the art. The resulting allyl ether (4) is treated in refluxing mesitylene or other suitable high boiling solvent to afford the desired Claisen rearrangement product. The 2-allyl phenol (5) intermediate is subjected to epoxidation of the double bond with 3-chloroperoxybenzoic acid in dichloromethane. The resulting epoxy phenol intermediate is treated with a suitable base such as potassium carbonate in a solvent such as methanol to induce cyclization to give the 2,3-dihydro-l-benzofuran-2- yl)methanol (6). Treatment of (6) with p-toluenesulfonyl chloride and a suitable base such as pyridine affords the tosylate (7). Conversion of (7) to the amine (1) can be accomplished, for example, by treatment with sodium azide in a solvent such as dimethylsulfoxide followed by reduction of the azide or direct treatment with an appropriately substituted amine to provide the compounds of Formula 1. Additionally, longer alkyl chains (i.e. 2-aminoethyl) may be prepared, for example, via treatment of (7) with sodium cyanide in a solvent such as dimethylsulfoxide followed by reduction of the nitrile.

The preparation of appropriately substituted phenols (2) in Scheme I, in particular the 7-aryl substituted phenols, is illustrated in Scheme Ia.

R ⁷ = I, Br, Cl, OTf

Scheme Ia

Utilization of a 2-halogenated methoxy benzene or a suitably protected 2- halogenated phenol (2a) permits the introduction of the aromatic substitutent through a palladium-catalyzed cross coupling reaction (i.e Suzuki reaction) with the desired boronic acid. Treatment of (2a) with a catalyst such as dichlorobis(tri-o-tolylphosphine)~ palladium(II) in the presence of a suitable base such as potassium carbonate in a solvent such as dioxane provides the biaryl system. Subsequent removal of the protecting group, in this example demethylation of (2b) via reaction with borontribromide in dichloromethane affords the phenol (2).

Alternatively, the phenols (2) may be prepared by a reversal of the inherent reactivity associated with the partners in the cross-coupling reaction as shown in Scheme Ib.

R' = B(OH) ₂

Scheme Ib

Installation of the biaryl system may also be accomplished via a palladium- catalyzed cross coupling reaction (i.e Suzuki reaction) of appropriate derivatives of 2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (7) with the desired boronic acid (Scheme Ic). Treatment of (7) with a catalyst such as dichlorobis(tri-o- tolylphosphine)-palladium(II) in the presence of a suitable base such as potassium carbonate in a solvent such as dioxane provides the biaryl system.

Alternatively, installation of the biaryl system may be accomplished via a palladium-catalyzed cross coupling reaction (i.e Suzuki reaction) of appropriate l-(2,3- dihydro-l-benzofuran-2-yl) derivatives (Ia) in either racemic or stereochemically pure form following separation of the enantiomers. For example, treatment of Ia and a boronic acid (Scheme Id) with a catalyst such as dichlorobis(tri-o-tolylphosphine)-palladium(II) in the presence of a suitable base such as potassium carbonate (as described previously) provides the desired biaryl system. Deprotection of the resultant product from the coupling procedure with, for example, iodotrimethylsilane in a solvent such as acetonitrile (foir X = NRCbz) then affords the title compounds of Formula 1.

X = OTs, Br, NRCbz bZ

Scheme Id

The compounds of Formula 1 can also be prepared in a stereoselective manner as illustrated in Scheme II.

Scheme II

Protection of the 2-allyl phenol (5) with a suitable protecting group such as benzyl by treatment with benzyl bromide in the presence of a suitable base such as potassium carbonate in a solvent such as N,N-dimethylformamide gives the benzyl ether (8). Treatment of (8) utilizing extant methodology known to one skilled in the art for the stereoselective oxidation of double bonds such as the Sharpless Asymmetric Dihydroxylation (A-D) provides the diol (9) in stereochemical^ enriched form. Many methods are available to one skilled in the art for the transfer of the stereochemical information present in (9) into the compounds of formula (1) with retention of

stereochemical integrity. One such method involves deprotection of the benzyl ether with catalytic palladium on carbon under a hydrogen atmosphere (45 psi) in a solvent, such as methanol, to provide triol (10). Formation to the previously described 2,3-dihydro-l- benzofuran-2-yl)methanol (6) can be accomplished by treatment of (9) with hydrogen bromide in acetic acid to provide the intermediate vicinal acetoxy bromide followed by cyclization with a suitable base such as potassium carbonate in a solvent such as methanol.

Alternatively, the compounds of Formula 1 can be prepared via selective mono- protection of diol (9) with a suitable protecting group as illustrated in Scheme III.

Scheme III

Treatment of (9) with fe/Y-butyldimethylsilyl chloride in the presence of a suitable base such as imidazole in a solvent such as N,N,-dimethylformamide followed by deprotection of the benzyl ether (as previously described) with catalytic palladium on carbon under a hydrogen atmosphere gives phenol (12). Cyclodehydration of (12) using standard Mitsunobu conditions, such as triphenylphosphine in the presence of diethylazodicarboxylate in a solvent such as toluene, provides the 2,3-dihydro-l- benzofuran-2-yl)methanol (13) protected as the silyl ether. Removal of the silyl ether in

(13) using standard conditions such as tetrabutylamonnium fluoride in a solvent such as tetrahydrofuran then provides the alcohol (6) which can be converted to the compounds of the current invention as previously described (Scheme I).

In lieu of a protecting group, diol (9) can be converted to the mono-tosylated derivative (12a) by treatment with p-toluenesulfonyl chloride and a suitable base such as pyridine to give the desired product, as illustrated in Scheme IV.

Scheme IV

Deprotection of the benzyl ether with catalytic palladium on carbon gives phenol (12b) followed by cyclodehydration with triphenylphosphine in the presence of diethylazodicarboxylate (as previously described) provides the aforementioned 2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (7).

An additional route to the production of stereochemically enriched compounds of Formula 1 is illustrated in Scheme V.

Scheme V

Palladium or transition metal catalyzed transposition of the double bond present in the previously described 2-allyl benzyl ether (8) using an appropriate catalyst such as dichlorobis(acetonitrile)palladium(II) in dichloromethane provides styrene derivative (14). Treatment of (14) with selenium dioxide in dioxane provides the carbonyl derivative (15). Reduction of the carbonyl to the allylic alcohol (16) can be accomplished by treatment with an appropriate reducing agent such as tetrabutylammonium borohydride in a solvent such as dichloromethane. The allylic alcohol (16) provides a suitable intermediate for the stereoselective introduction of oxygenation that permits transfer of this stereochemical integrity into the compounds of formula (1). The Sharpless Asymmetric Epoxidation (A-E) reaction is a general method for the stereoselective epoxidation of allylic alcohols and treatment of (16) under the appropriate conditions provides epoxy alcohol (17) with a high degree of stereoselectivity. The alcohol present in (17) can then be tosylated with p-toluenesulfonyl chloride as previously described to give derivative (18). Deprotection of the benzyl ether with concomitant regioselective opening of the epoxide maintaining the stereochemical information introduced by the Sharpless A-E is accomplished under the appropriate conditions by treatment of (18) with

palladium on carbon under a hydrogen atmosphere in a solvent such as ethanol. Cyclodehydration using Mitsunobu conditions as previously described then affords 2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (7).

The preparation of compounds of Formula 1 can also be accomplished in a stereospecific manner utilizing an optically pure commercially available intermediate. This method is described in detail in a copending U.S. provisional patent application entitled "Process For Stereospecific Synthesis of Dihydrobenzofuran Derivatives," filed in the name of Daliui Zhou, et al. on the same date as the instant application. That application is incorporated herein by reference in its entirety for all purposes. As shown in Scheme VI, below, for example, reaction of benzyl (S)-(+)-glycidyl ether with the anion obtained by treatment of 2-bromoanisole with an alkyllithium such as n- butyllithium provides the resultant epoxy intermediate. Ring opening of the epoxide with a Lewis acid such as borontrifluoride diethyletherate provides diol (9a) with the primary alcohol protected as the benzyl ether. Deprotection of the methoxy group in 9a by treatment with 30% hydrogen bromide in acetic acid results in concomitant formation of intermediate vicinal acetoxy bromide (10a) followed by removal of the acetate with aqueous hydrogen chloride to provide diol (13a). Cyclodehydration with triphenylphosphine in the presence of diethylazodicarboxylate (as previously described) provides the desired 2-(bromomethyl)-2,3-dihydro-l-benzofuran (7b) that can be converted to the 7-bromo derivative (7c) by treatment with bromine in acetic acid.

A further method for the synthesis of stereochemically enriched compounds of Formula 1 is described in detail in copending U.S. provisional patent application

60/621,024, filed October 21, 2004 entitled "Asymmetric Synthesis of 2- (methylamino)dihydrobenzofurans," filed in the name of Alexander Gontcharov, et al. That application is incorporated herein by reference in its entirety for all purposes. That method is illustrated in the preparation of the compound 2R-(-)-7-(2,6-dichlorophenyl)-5- fluoro-2,3-dihydro-2-aminomethylbenzofuran hydrochloride shown in Scheme VII.

Step i Step 2

Step 5

MsCI, NEt ₃ CH ₂ CI ₂

Scheme VII

An additional method for the synthesis of stereochemically enriched compounds of Formula 1 is described in detail in copending U.S. provisional patent application entitled "Asymmetric Synthesis of 2-(methylamino)dihydrobenzofurans," filed in the name of Alexander Gontcharov, et al. on the same date as the instant application. That application is incorporated herein by reference in its entirety for all purposes. That method is also illustrated in the preparation of the compound 2R-(-)-7-(2,6- dichlorophenyl)-5-fluoro-2,3-dihydro-2-aminomethylbenzofuran hydrochloride shown in Scheme IX.

Scheme IX

Step 8a

HCl (IPA solution) 80% for two steps

In certain embodiments, the invention relates to compositions comprising at least one compound of Formula 1, or a pharmaceutically acceptable salt thereof, and one or more pharmaceutically acceptable carriers, excipients, or diluents. Such compositions are prepared in accordance with acceptable pharmaceutical procedures, such as, for example, those described in Remingtons Pharmaceutical Sciences, 17th edition, ed. Alfonoso R. Gennaro, Mack Publishing Company, Easton, PA (1985), which is incorporated herein by reference in its entirety. Pharmaceutically acceptable carriers are those carriers that are compatible with the other ingredients in the formulation and are biologically acceptable. The compounds of Formula 1 can be administered orally or parenterally, neat, or in combination with conventional pharmaceutical carriers. Applicable solid carriers can include one or more substances that can also act as flavoring agents, lubricants,

solubilizers, suspending agents, fillers, glidants, compression aids, binders, tablet- disintegrating agents, or encapsulating materials. In powders, the carrier is a finely divided solid that is in admixture with the finely divided active ingredient. In tablets, the active ingredient is mixed with a carrier having the necessary compression properties in suitable proportions and compacted in the shape and size desired. The powders and tablets preferably contain up to 99% of the active ingredient. Suitable solid carriers include, for example, calcium phosphate, magnesium stearate, talc, sugars, lactose, dextrin, starch, gelatin, cellulose, methyl cellulose, sodium carboxymethyl cellulose, polyvinylpyrrolidine, low melting waxes and ion exchange resins. Liquid carriers can be used in preparing solutions, suspensions, emulsions, syrups and elixirs. The active ingredient can be dissolved or suspended in a pharmaceutically acceptable liquid carrier such as water, an organic solvent, a mixture of both, or a pharmaceutically acceptable oil or fat. The liquid carrier can contain other suitable pharmaceutical additives such as, for example, solubilizers, emulsifiers, buffers, preservatives, sweeteners, flavoring agents, suspending agents, thickening agents, colors, viscosity regulators, stabilizers or osmo-regulators. Suitable examples of liquid carriers for oral and parenteral administration include water (particularly containing additives as above, e.g. cellulose derivatives, preferably sodium carboxymethyl cellulose solution), alcohols (including monohydric alcohols and polyhydric alcohols e.g. glycols) and their derivatives, and oils (e.g. fractionated coconut oil and arachis oil). For parenteral administration, the carrier can also be an oily ester such as ethyl oleate and isopropyl myristate. Sterile liquid carriers are used in sterile liquid form compositions for parenteral administration. The liquid carrier for pressurized compositions can be halogenated hydrocarbon or other pharmaceutically acceptable propellant. Liquid pharmaceutical compositions that are sterile solutions or suspensions can be administered by, for example, intramuscular, intraperitoneal or subcutaneous injection. Sterile solutions can also be administered intravenously. Compositions for oral administration can be in either liquid or solid form.

The compounds of Formula 1 can be administered rectally or vaginally in the form of a conventional suppository. For administration by intranasal or intrabronchial inhalation or insufflation, the compounds of Formula 1 can be formulated into an aqueous or partially aqueous solution, which can then be utilized in the form of an aerosol. The

compounds of Formula 1 can also be administered transdermally through the use of a transdermal patch containing the active compound and a carrier that is inert to the active compound, is non-toxic to the skin, and allows delivery of the agent for systemic absorption into the blood stream via the skin. The carrier can take any number of forms such as creams and ointments, pastes, gels, and occlusive devices. The creams and ointments can be viscous liquid or semisolid emulsions of either the oil-in- water or water- in-oil type. Pastes comprised of absorptive powders dispersed in petroleum or hydrophilic petroleum containing the active ingredient can also be suitable. A variety of occlusive devices can be used to release the active ingredient into the blood stream such as a semipermeable membrane covering a reservoir containing the active ingredient with or without a carrier, or a matrix containing the active ingredient. Other occlusive devices are known in the literature.

Preferably the pharmaceutical composition is in unit dosage form, e.g. as tablets, capsules, powders, solutions, suspensions, emulsions, granules, or suppositories. In such form, the composition is sub-divided in unit dose containing appropriate quantities of the active ingredient; the unit dosage forms can be packaged compositions, for example, packeted powders, vials, ampoules, prefilled syringes or sachets containing liquids. The unit dosage form can be, for example, a capsule or tablet itself, or it can be the appropriate number of any such compositions in package form. The amount of compound of formula 1 provided to a patient will vary depending upon what is being administered, the purpose of the administration, such as prophylaxis or therapy, the state of the patient, the manner of administration, and the like. In therapeutic applications, compounds of formula 1 are provided to a patient suffering from a condition in an amount sufficient to treat or at least partially treat the symptoms of the condition and its complications. An amount adequate to accomplish this is a

"therapeutically effective amount" as described previously herein. The dosage to be used in the treatment of a specific case must be subjectively determined by the attending physician. The variables involved include the specific condition and the size, age, and response pattern of the patient. The treatment of substance abuse follows the same method of subjective drug administration under the guidance of the attending physician. Generally, a starting dose is about 5 mg per day with gradual increase in the daily dose to about 150 mg per day, to provide the desired dosage level in the patient.

In certain embodiments, the present invention is directed to prodrugs of compounds of Formula 1. The term "prodrug," as used herein, means a compound that is convertible in vivo by metabolic means (e.g. by hydrolysis) to a compound of Formula 1. Various forms of prodrugs are known in the art such as those discussed in, for example, Bundgaard, (ed.), Design of Prodrugs, Elsevier (1985); Widder, et al. (ed.), Methods in Enzymology, vol. 4, Academic Press (1985); Krogsgaard-Larsen, et al., (ed). "Design and Application of Prodrugs, Textbook of Drug Design and Development, Chapter 5, 113-191 (1991), Bundgaard, et al., Journal of Drug Delivery Reviews, 8:1-38(1992), Bundgaard, J. of Pharmaceutical Sciences, 77:285 et seq. (1988); and Higuchi and Stella (eds.) Prodrugs as Novel Drug Delivery Systems, American Chemical Society (1975), each of which is hereby incorporated by reference in its entirety.

Intermediate 1: l-allyl-2-(benzyloxy)-4-methoxybenzene

To a solution of 2-allyl-5-methoxyphenol (20.30 g, 0.124 mol) in DMF (500 niL) was added potassium carbonate (68.35 g, 0.495 mol) followed by benzyl bromide (23.26 g, 0.136 mol) and tetrabutylammonium iodide (4.57 g, 0.012 mol). The reaction mixture was allowed to stir at room temperature for 12 h. The reaction mixture was diluted with water (1000 mL) to dissolve any solids and extracted with diethyl ether (3 x 250 mL). The combined organic layers were washed with water (4 x 500 mL), saturated aqueous sodium chloride (400 mL), dried (magnesium sulfate) and the solvent removed in vacuo to give a crude oil. Purification by flash column chromatography (silica, ethyl acetate:hexanes 1:19) provided 28.44 g (90%) of l-allyl-2-(benzyloxy)-4- methoxybenzene as a colorless oil. Ry= 0.88 (silica, ethyl acetate :hexanes 1 :9); Anal. calcd. for Ci ₇ Hi ₈ O ₂ : C, 80.28; H, 7.13. Found: C, 82.43; H, 7.09.

Intermediate 2: (±)-3-[2-(benzyIoxy)-4-methoxyphenyl]propane-l,2-diol

To a suspension of AD-mix-α (156.55 g) in water: tert-butyl alcohol (1 :1, 800 mL) cooled to 0 ⁰ C was slowly added via an addition funnel a solution of l-allyl-2- (benzyloxy)-4-methoxybenzene (28.44 g, 0.112 mol) in water: tert-butyl alcohol (1 :1, 200 mL) and the reaction mixture was allowed to stir at 0 °C for 12 h. The reaction mixture was quenched by the addition of sodium sulfite. The reaction mixture was diluted with water (500 mL) and ethyl acetate (500 mL). The aqueous phase was separated and

extracted with ethyl acetate (2 x 200 niL). The combined organic extracts were washed with saturated aqueous sodium chloride (400 mL), dried (magnesium sulfate) and the solvent was removed in vacuo to give a crude oil. Purification by flash column chromatography (silica, ethyl acetate :hexanes 3:2) gave 30.50 g (95%, 27% ee) of (±)-3- [2-(benzyloxy)-4-methoxyphenyl]propane-l,2-diol as a white crystalline solid, mp 82-86 ⁰ C; Anal, calcd. for C17H20O4: C, 70.81; H, 6.99. Found: C, 70.78; H, 7.16.

Intermediate 3: (±)-3-[2-(benzyloxy)-4-methoxyphenyl]-2-hydroxypropyl 4- methylbenzenesulfonate To a solution of (±)-3-[2-(benzyloxy)-4-methoxyphenyl]propane-l,2-diol (30.50 g, 0.106 mol) in anhydrous pyridine (600 mL) cooled to 0 °C under a nitrogen atmosphere was added p-toluenesulfonyl chloride (22.18 g, 0.116 mol). The reaction mixture was allowed to stir at 0 °C for 12 h. The reaction mixture was quenched by the addition of water (10 mL). The reaction mixture was diluted with ethyl acetate (750 mL) and the organic layer was washed with aqueous hydrogen chloride (6 N, 4 x 400 mL), saturated aqueous sodium chloride (300 mL), dried (magnesium sulfate) and the solvent was removed in vacuo to give a crude oil. Purification by flash column chromatography (silica, ethyl acetate :hexanes 2:8) gave 42.84 g (91%) of (±)-3-[2-(benzyloxy)-4- methoxyphenyl]-2-hydroxypropyl 4-methylbenzenesulfonate as a colorless oil. R/= 0.28 (silica, ethyl acetate :hexanes 2:8); Anal, calcd. for C24H26O6S: C, 65.14; H, 5.92. Found: C, 64.59; H, 5.72.

Intermediate 4: (±)-2-hydroxy-3-(2-hydroxy-4-methoxyphenyl)propyl 4- methylbenzenesulfonate To a solution of (±)-3-[2-(benzyloxy)-4-methoxyphenyl]-2-hydroxypropyl 4- methylbenzenesulfonate (42.84 g, 0.097 mol) in ethanol (600 mL) was added palladium on carbon (10 wt.%, 5.81 g) and the reaction mixture was shaken under an H2 atmosphere

(50 psi) for 6 h. The reaction mixture was filtered (celite) and the solvent removed in vacuo to provide 32.27 g (95%) of (±)-2-hydroxy-3-(2-hydroxy-4-methoxyphenyl)propyl 4-methylbenzenesulfonate as a colorless oil. 0.34 (silica, ethyl acetate :hexanes 2:8);

Anal, calcd. for Ci ₇ Hi ₈ O ₅ S: C, 61.06; H, 5.43. Found: C, 60.70; H, 5.37.

Intermediate 5: (±)-(6-methoxy-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate

To a solution of (±)-2-hydroxy-3-(2-hydroxy-4-methoxyphenyl)propyl 4- methylbenzenesulfonate (32.27 g, 0.092 mol) in toluene (1000 niL) cooled to 0 °C was added triphenylphosphine (27.62 g, 0.105 mol) followed by dropwise addition of diethylazodicarboxylate (18.34 g, 0.105 mol) and the reaction mixture was allowed to stir at 0 ⁰ C for 15 min. The reaction mixture was quenched by the addition of water (10 mL). The solvent was removed in vacuo to give a crude solid. Purification by flash column chromatography (silica, ethyl acetate :hexanes 1 :19) provided 22.53 g (74%) of (±)-(6- methoxy-2,3-dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate as a colorless oil. Rf= 0.67 (silica, ethyl acetate :hexanes 1:9); Anal, calcd. for CiγHigOsS: C, 61.06;

H, 5.43. Found: C, 60.70; H, 5.37.

Intermediate 6: (±)-(6-hydroxy-2,3-dihydro-l-benzofuran-2~yI)methyl 4- methylbenzenesulfonate

To a solution of (±)-(5-methoxy-2,3-dihydro-lH-inden-2-yl)methyl 4- methylbenzenesulfonate (13.5 g, 40.5 mniol) in dichloromethane (250 mL) at -70 ⁰ C was added boron tribromide (27.0 mL, 1.0 N in dichloromethane) over 15 min. The reaction mixture was allowed to stir at -70 °C for an additional 15 minutes and allowed to warm to room temperature over 6 h. The reaction mixture was quenched with ice water and the product extracted with ethyl acetate (600 mL). The organic layer dried (magnesium sulfate), and the solvent removed in vacuo to provide a crude oil. Purification by flash column chromatography (silica, ethyl acetate :hexanes 1 :4→1 :1) afforded 10.15 g (79%) of (±)-(6-hydroxy-2,3-dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate as a yellow solid, mp 107-110 °C; Anal, calcd. for Ci6Hi ₆ O ₅ S: C ₅ 59.99; H, 5.03. Found: C, 59.21; H, 5.05.

Intermediate 7: (±)-(6-phenyI~2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate To a solution of (±)-(6-hydroxy-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate (8.67 g, 27.2 mmol) in anhydrous dichloromethane (300 mL) at 0 ⁰ C was added diisopropylethylamine (4.22 g, 32.6 mmol) followed by

trifluoromethanesulfonic anhydride (8.45 g, 29.9 mniol) and the reaction mixture was allowed to stir at 0 ⁰ C for 1 h. The reaction mixture was quenched with water (300 mL) and diluted with dichloromethane (400 mL), The combined organic layers were washed with saturated aqueous sodium chloride, dried (magnesium sulfate), and the solvent removed in vacuo to provide a crude solid. Purification by flash column chromatography (silica, ethyl acetate :hexanes 1:4→2:3) afforded 10.3 g (84%) of (±)-(6- {[(trifluoromethyl)sulfonyl]oxy}-2,3-dihydro-l-benzofuran-2- yl)methyl 4- methylbenzenesulfonate as a tan solid. To a solution of (±)-(6- {[(trifluoromethyl)sulfonyl]oxy}-2,3-dihydro-l-benzofuran-2- yl)methyl 4- methylbenzenesulfonate (2.0 g, 4.43 mmol) in dioxane (50 mL) was added phenylboronic acid (1.08 g, 8.86 mmol), tetrakis(triphenylphosphine)palladium(0) (1.0 g, 0.884 mmol), and lithium chloride (0.787 g, 17.43 mmol) and the reaction mixture was heated at 90 ⁰ C for 12 h. The reaction mixture was cooled to room temperature and diluted with water (500 mL) and ethyl acetate (500 mL). The organic layer was separated and washed with water (200 mL), saturated aqueous sodium chloride (200 mL), dried (magnesium sulfate) and the solvent removed in vacuo to give a crude solid. Purification by flash column chromatography (silica, ethyl acetate :hexanes 1 :9) provided 0.17O g (10%) of (±)-(6- phenyl-2,3-dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate as an oil. ¹ H NMR (DMSO d ₆ ) δ _H 7.75 (d, 2H); 7.56 (d, 2H); 7.42 (m, 4H); 7.28(t, IH); 7.21 (d, IH); 7.08 (d, IH); 6.92 (s, IH); 4.98 (m, IH); 4.24 (dd, IH); 4.18 (q, IH); 3.29 (dd, IH); 2.88 (dd, IH); 2.46 (s, 3H).

Intermediate 8: 2-allyl-6-chloro-3-(trifluoromethyl)phenoI

To a solution of 2-chloro-5-trifluorornethyl-phenol (10.00 g, 0.05 mol) in N ₁ N- dimethylformamide (500 mL) was added potassium carbonate (28.12 g, 0.209 mol) followed by allyl bromide (7.38 g, 0.061 mol) and the reaction was allowed to stir at room temperature for 12 h. The reaction mixture was diluted with water (500 mL) to dissolve any solids and extracted with ethyl acetate (3 x 250 mL). The combined organic layers were washed with water (4 x 500 mL), saturated aqueous sodium chloride (400 mL), dried (magnesium sulfate) and the solvent removed in vacuo to give 2-(allyloxy)-l- chloro-4-(trifluoromethyl)benzene as a colorless oil. The oil was re-dissolved in mesitylene (35 mL) and heated at reflux for 12 h. Removal of the solvent in vacuo

provided a crude oil. Purification by flash column chromatography (silica, ethyl acetate:hexanes 2:8) provided 9.6 g (96%) of 2-allyl-6-chloro-3-(trifluoromethyl)phenol as a amber oil. 0.66 (silica, ethyl acetate:hexanes 1:4); ¹ H NMR (DMSO-d ₆ ) δ _H 9.84 (s, IH); 7.43 (d, 2H); 7.16 (d, IH); 5.84 (m, IH); 4.95 (d, IH); 4.89 (d, IH); 3.46 (d, 2H).

Intermediate 9: (±)-[7-chloro-4-(trifluoromethyl)-2,3-dihydro-l-benzofuran- 2- yl] methanol

To a solution of 6-chloro-3-(trifluoromethyl)-2-vinylphenol (9.67 g, 0.043 mol) in dichloromethane 225 mL) was added 3-chloroperoxybenzoic acid (77%, 21.15 g, 0.122 mol). The reaction mixture was allowed to stir at room temperature for 8 h. The reaction mixture was washed with a 1:1 solution of 10% sodium sulfite:saturated sodium bicarbonate (2 x 200 mL). The solvent was removed in vacuo to give crude yellow oil. The oil was diluted with methanol (100 mL) and added to a solution of potassium carbonate (16.5 g, 0.119 mol) and methanol (825 mL) and the solution was allowed to stir at room temperature 2 h. The solvent was removed in vacuo. The residue was washed with water (1000 mL) and ethyl acetate (500 mL). The aqueous layer was acidified with 1 N aqueous hydrogen chloride and washed with ethyl acetate (500 mL). The combined organics were washed with water (500 mL), saturated aqueous sodium chloride (500 mL), dried (magnesium sulfate) and the solvent removed in vacuo to provide a crude solid. Purification by flash column chromatography (silica, ethyl acetate :hexanes 1 :4) provided 6.71 g (70%) of (±)-(7-bromo-4-fluoro-2,3-dihydro-l-benzofuran-2-yl)methano l as a yellow oil. 0.20 (silica, ethyl acetate :hexanes 1 :4). Anal, calcd. for CioHgClF3θ2 C,

47.55; H, 3.19. Found C, 49.39; H, 3.57.

Intermediate 10: (±)-[7-chloro-4-(trifluoromethyl)-2,3-dihydro-l~benzofuran- 2- yl]methyl 4-methylbenzenesulfonate

To a solution of (±)-(7-bromo-4-fluoro-2,3-dihydro-l-benzofuran-2-yl)methano l (8.5, g, 0.034 mol) in pyridine (150 mL) cooled to 0 °C was added p-toluenesulfonyl chloride (7.06 g, 0.037 mol) and the reaction mixture was allowed to stir at 0 °C for 12 h. The reaction mixture was quenched by the addition of water (75 mL), diluted with diethyl ether (600 mL), washed with aqueous hydrogen chloride (1.0 M, 750 mL), water (200 mL), saturated aqueous sodium chloride (200 mL), dried (magnesium sulfate) and the

solvent removed in vacuo to give a crude oil. Purification by flash column chromatography (silica, ethyl acetate :hexanes 2:8) afforded 7.Og (51%) of (±)-[7-chloro- 4-(trifluoromethyl)-2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate as a white solid Ry= 0.60 (silica, ethyl acetate:hexanes 3:7); mp 89-92 °C; Anal, calcd. for C ₁₇ H ₁₄ ClF ₃ O ₄ S C, 50.19; H, 3.47. Found C ₅ 50.30; H ₅ 3.35.

Intermediate 11: (±)-(7-cyclopentyl-2,3-dihydro-l-benzofuran-2-yl)methanol

Treatment of 2-allyl-6-cyclopentylphenol (6.97 g, 0.0344 mol) with 3- chloroperoxybenzoic acid (17.83 g, 0.1033 mol, 77%) and potassium carbonate (14.0 g, 0.1013 mol) generally according to the procedure described for Intermediate 9 afforded 4.1 g (54%) of (±)-(7-cyclopentyl-2,3-dihydro-l-benzofuran-2-yl)methanol as a yellow oil. Ry= 0.58 (silica, ethyl acetate :hexanes 3:7); Anal, calcd. for C ₁₄ H ₁ gC^ C ₅ 77.03; H ₅

8.31. Found C ₅ 76.5; H ₅ 8.44.

Intermediate 12: (±)-benzyl (7-cyclopentyl-2,3-dihydro-l-benzofuran-2- yl)methylcarbamate

To a suspension of (7-cyclopentyl-2,3-dihydro-l-benzofuran-2-yl)methylamine (2.4g, 9.46 mmol) in tetrahydrofuran (10OmL) cooled to 0 ⁰ C was added diisopropylethylamine (2.14 g ₅ 16.58 mmol) followed by benzyl chloroformate (2.08g, 12.19 mmol) and the reaction mixture was allowed to stir for 15 min. The reaction mixture was quenched with water (100 mL). The aqueous layer was extracted with ethyl acetate (2 x 200 mL) and the combined organic extracts were washed with saturated aqueous sodium chloride (100 mL), dried (magnesium sulfate) and the solvent removed in vacuo. Purification by flash column chromatography (silica, ethyl acetate :hexanes 1 :9) provided 2.52 g (76%) of (±)-benzyl (7-cyclopentyl-2,3-dihydro-l-benzofuran-2- yl)methylcarbamate as a yellow oil. Ry= 0.21 (silica, ethyl acetate :hexanes 2:8); Anal, calcd. for C22H25NO3 C, 75.19; H, 7.17; N, 3.99. Found C, 74.74; H, 7.02; N ₅ 3.85.

Chiral HPLC separation of (±)-benzyl (7-cyclopentyl-2 ₅ 3-dihydro-l-benzofuran-2- yl)methylcarbamate (Chiralcel OJ, ethanol:hexane 1 :1) provided two fractions. Fraction 1 (Rf = 9.678 min, Chiralcel OJ, ethanohhexane 1 :1); Fraction 2 (R _t = 12.824 min, Chiralcel OJ ₅ ethanohhexane 1:1).

Intermediate 13: (±)-(5-chloro-7-cyclohexyl-2,3-dihydro-l-benzofuran-2- yl)methanol

To a solution of 4-chloro-2-cyclohexylphenol (23.00 g, 0.109 mol) wN,N- dimethylformamide (600 niL) was added sodium hydride (4.56 g, 0.114 mol, 60 wt.%) followed by allyl bromide (14.51 g, 0.120 mol) and the reaction mixture was allowed to stir at room temperature for 5 h. The solvent was removed in vacuo and the residue diluted with water (500 mL) and extracted with ethyl acetate (2 x 300 mL). The combined organic layers were washed with water (500 mL), saturated aqueous sodium chloride (500 mL), dried (magnesium sulfate), and the solvent removed in vacuo to give 29.0 g of 1- (allyloxy)-4-chloro-2-cyclohexylbenzene as a brown oil. Treatment of the allyl ether in refluxing mesitylene generally according to the procedure described for Intermediate 8 provided 18.0 g of 2-allyl-4-chloro-6-cyclohexylphenol. Treatment of the phenol (6.5 g, 0.026 mol) with 3-chloroperoxybenzoic acid (9.88 g, 0.045 mol, 77%) followed by potassium carbonate (10.00 g, 0.072 mol) generally according to the procedure described for Intermediate 9 afforded 4.6 g (67%) of (±)-(5-chloro-7-cyclohexyl-2,3-dihydro-l- benzofuran-2-yl)methanol as a white solid, mp 67-69 °C; Anal, calcd. for C15H19CIO2:

C, 67.54; H, 7.18. Found: C, 67.81; H, 6.98.

Intermediate 14: (±)-methyl (5-chloro-7-cyclohexyl-2,3-dihydro-l-benzofuran-2- yl)methylcarbamate

Treatment of (±)-(5-chloro-7-cyclohexyl-2,3-dihydro-l-benzofuran-2- yl)methylamine (2.20 g, 7.28 mmol) with diisopropylethylamine (2.94 g, 22.7 mmol) and methyl chloroformate (1.08 g, 11.4 mmol) generally according to the procedure described for Intermediate 12 provided 2.30 g (93%) of (±)-methyl (5-chloro-7-cyclohexyl-2,3- dihydro-l-benzofuran-2-yl)methylcarbamate as a white solid, mp 100-103 °C; Anal, calcd. for C ₁₇ H^ClNO ₃ : C, 63.06; H, 6.85; N, 4.33. Found: C ₅ 63.16; H, 6.3; N, 4.25.

Intermediate 15: (±)-3-[3-benzyl-2-(benzyloxy)phenyl]propane-l,2-dioI

Treatment of 2-allyl-6-benzylphenol (12.11 g, 0.054 mol) with potassium carbonate (30.00 g, 0.217 mol), benzyl bromide (10.67 g, 0.062 mol), and tetrabutylammonium iodide (2.01 g, 0.005 mol) generally according to the procedure described for Intermediate 1 provided l-allyl-3-benzyl-2-(benzyloxy)benzene. Treatment

of l-allyl-3-benzyl-2-(benzyloxy)benzene (16.35 g, 0.052 mol) with AD-mix-α (76.02 g) generally according to the procedure described for Intermediate 2 gave 9.82 (54%, 25% ee) of (±)-3-[3-benzyl-2-(benzyloxy)phenyl]propane-l,2-diol as a white crystalline solid, mp 55-58 °C; Anal, calcd. for C23H24O3: C, 79.28; H, 6.94. Found: C, 78.89; H, 6.96.

Intermediate 16: (±)-3-[3-benzyl-2-(benzyloxy)phenyl]-2-hydroxypropyl 4- methylbenzenesulfonate

Treatment of (±)~3-[3-benzyl-2-(benzyloxy)phenyl]propane-l,2-diol (9.76 g, 0.028 mol) with^-toluenesulfonyl chloride (5.87 g, 0.031 mol) in pyridine (250 mL) generally according to the procedure described for Intermediate 3 gave 9.88 g (70%) of (±)-3-[3-benzyl-2-(benzyloxy)phenyl]-2-hydroxypropyl 4-methylbenzenesulfonate as a colorless oil. Anal, calcd. for C30H30O5S: C, 71.69; H, 6.02. Found: C, 70.41; H, 6.14.

Intermediate 17: (±)-3-(3-benzyl-2-hydroxyphenyl)-2-hydroxypropyl 4- methylbenzenesulfonate

Treatment of (±)-3-[3-benzyl-2-(benzyloxy)phenyl]-2-hydroxypropyl A- methylbenzenesulfonate (9.72 g, 0.019 mol) with palladium on carbon (0.97 g, 10 wt.%) generally according to the procedure described for Intermediate 4 provided 7.34 g (92%) of (±)-3-(3-benzyl-2-hydroxyphenyl)-2-hydroxypropyl 4-methylbenzenesulfonate as a colorless oil. Anal, calcd. for C23H24O5S: C, 66.97; H, 5.86. Found: C, 66.11; H, 5.95.

Intermediate 18: (±)-(7-benzyl-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate

Treatment of (±)-3-(3-benzyl-2-hydroxyphenyl)-2-hydroxypropyl A- methylbenzenesulfonate (7.29 g, 0.018 mol) with triphenylphosphine (5.10 g, 0.019 mol) and diethylazodicarboxylate (3.39 g, 0.019 mol) generally according to the procedure described for Intermediate 5 afforded 6.57 g (94%) of (±)-(7-benzyl-2,3-dihydro~l- benzofuran-2-yl)methyl 4-methylbenzenesulfonate as a colorless oil. Anal, calcd. for C23H22O4S: C ₅ 70.03; H, 5.62. Found: C, 68.97; H, 5.42.

Intermediate 19: (±)-benzyl (7-benzyI-2,3-dihydro-l-benzofuran-2- yl)methylcarbamate

Treatment of (±)-l-(7-benzyl-2,3-dihydro-l-benzofuran-2-yl)methanamine (2.0 g, 8.36 mmol) with diisopropylethylamine (1.62 g, 12.56 mmol) and benzyl chloroformate (1.64 g, 9.61 mmol) generally according to the procedure described for Intermediate 12 provided 2.96 g (95%) of (±)-benzyl (7-benzyl-2,3-dihydro-l-benzofuran-2- yl)methylcarbamate as a colorless oil. Anal, calcd. for C24H23NO3 C, 77.19; H, 6.21; N,

3.75. Found C, 75.58; H, 6.42; N, 3.55. Chiral HPLC eparation of (±)-benzyl (7-benzyl- 2,3-dihydro-l-benzofuran-2-yl)methylcarbamate (Chiralcel OD, methanol) provided two fractions. Fraction 1 (R _t = 12.085 min, Chiralcel OD, methanol); Fraction 2 (R, = 17.945 min, Chiralcel OD, methanol).

Intermediate 20: (±)-(7-isopropyI-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate Treatment of 2-allyl-6-isopropylphenol (8.81 g, 0.05 mmol) with 3- chloroperoxybenzoic acid (22.43 g, 0.13 mol, 77%) ) followed by potassium carbonate (13.82 g, 0.1 mol) generally according to the procedure described for Intermediate 9 provided (±)-(7-isopropyl-2,3-dihydro-l-benzofuran-2-yl)methanol. Treatment of (±)-(7- isopropyl-2,3-dihydro-l-benzofuran-2-yl)methanol (3.45 g, 0.018 mol) withp- toluenesulfonyl chloride (3.92 g, 0.021 mol) generally according to the procedure described for Intermediate 10 afforded 4.91 g (79%) (±)-(7-isopropyl-2,3-dihydro-l- benzofuran-2-yl)methyl 4-methylbenzenesulfonate as a colorless oil. Anal, calcd. for C ₁₉ H ₂ 2θ ₄ S C, 65.87; H, 6.4. Found C, 65.63; H, 6.32.

Intermediate 21: (±)-benzyl (7-isopropyl-2,3-dihydro-l-benzofuran-2- yl)methylcarbamate

Treatment of (±)-(7-isopropyl-2,3-dihydro-l-benzofuran-2-yl)methylamine (2.2 g, 9.66 mmol) with diisopropylethylamine (3.12 g, 24.15 mmol) and benzyl chloroformate (1.81 g, 10.63 mmol) generally according to the procedure described for Intermediate 12 gave 1.2 g (59%) of (±)-benzyl (7-isopropyl-2,3-dihydro-l -benzofuran-2- yl)methylcarbamate as a colorless oil. Anal, calcd. for C20H23NO3 C, 73.82; H, 7.12; N,

4.3. Found C, 73.32; H, 7.33; N, 4.15. Chiral HPLC separation of (±)-benzyl (7-

isopropyl-2,3-dihydro-l-benzofuran-2-yl)methylcarbamate (Chiralcel OJ ₃ ethanol) provided two fractions. Fraction 1 (R^ = 9.319 min, Chiralcel OJ, ethanol); Fraction 2 (R _t

= 11.868 min, Chiralcel OJ, ethanol).

Intermediate 22: 2-allyI-4-chloro-6-isopropyI-3-methylphenol

Treatment of 4-chloro-2-isopropyl-5-methylphenol (10.00 g, 0.054 mol) with potassium carbonate (29.94 g, 0.217 mol) and allyl bromide (7.86 g, 0.065 mol), followed by refluxing the resultant allyl ether in mesitylene generally according to the procedure described for Intermediate 8 provided 8.92 g (73%) of 2-allyl-4-chloro-6-isopropyl-3- methylphenol as a colorless oil. Ry= 0.85 (silica, ethyl acetate :hexanes 1 :9); Anal, calcd. for Ci ₃ H ₁₇ ClO: C ₅ 69.48; H, 7.62. Found: C, 69.87; H, 7.43.

Intermediate 23: (±)-(5-chloro-7-isopropyl-4-methyl-2,3-dihydro-l-benzofuran -2- yl)methyl 4-methylbenzenesulfonate Treatment of 2-allyl-4-chloro-6-isopropyl-3 -methylphenol (8.88 g, 0.04 mmol) with 3-chloroperoxybenzoic acid (13.63 g, 0.079 mol, 77%) ) followed by potassium carbonate (10.92 g, 0.079 mol) generally according to the procedure described for Intermediate 9 provided (±)-(5-chloro-7-isopropyl-4-methyl-2,3-dihydro-l-benzofuran -2- yl)methanol. Treatment of (±)-(5-chloro-7-isopropyl-4-methyl-2,3-dihydro-l-benzofuran - 2-yl)methanol (5.95 g, 0.025 mol) with/7-toluenesulfonyl chloride (5.66 g, 0.03 mol) generally according to the procedure described for Intermediate 10 afforded 6.71 g (69%) (±)-(5-chloro-7-isopropyl-4-methyl-2,3-dihydro-l-benzofuran -2-yl)methyl 4- methylbenzenesulfonate as a white solid, mp 103-105 °C; Anal, calcd. for C20H23CIO4S

C, 60.83; H, 5.87. Found C, 60.67; H, 5.88.

Intermediate 24: (±)-benzyl (5-chloro~7-isopropyl-4-methyl-2,3-dihydro-l- benzofuran-2-yl)methyIcarbamate

Treatment of (±)- 1 -(5-chloro-7-isopropyl-4-methyl-2,3 -dihydro- 1 -benzofuran-2- yl)methanamine (3.41 g, 12.3 mmol) with diisopropylethylamine (1.99 g, 14.2 mmol) and benzyl chloroformate (2.42 g, 14.2 mmol) generally according to the procedure described for Intermediate 12 gave 3.74 g (81%) of (±)-benzyl (5-chloro-7-isoρropyl-4-methyl-2,3- dihydro-l-benzofuran-2-yl)methylcarbamate as a colorless oil. Anal, calcd. for

C21H24CINO3 C, 67.46; H ₅ 6.47; N, 3.75. Found C, 67.01; H, 6.52; N ₅ 3.56. Chiral HPLC separation of (±)-benzyl (5-chloro-7-isopropyl-4-methyl-2 ₅ 3-dihydro-l- benzofuran-2-yl)methylcarbamate (Chiralpak AD ₅ ethanol) provided two fractions.

Intermediate 25: (-)-benzyl (5-chIoro-7-isopropyl-4-methyl-2,3-dihydro-l- benzofuran-2-yl)methylcarbamate

Fraction 1 obtained as a white solid from the separation of (±)-benzyl (5-chloro-7- isopropyl-4-methyl-2,3-dihydro-l-benzofuran-2-yl)methylcarba mate (R^ = 4.132 min,

Chiralpak AD, ethanol). [άffi = -38.52 (c 10.0 in methanol); mp 59-62 °C; Anal, calcd. for C21H24CINO3 C, 67.46; H, 6.47; N ₅ 3.75. Found C, 67.26; H ₅ 6.41; N ₅ 3.36.

Intermediate 26: (+)-benzyl (5-chloro-7-isopropyl-4-methyl-2,3-dihydro-l- benzofuran-2-yl)methylcarbamate

Fraction 2 obtained as a white solid from the separation of (±)-benzyl (5-chloro-7- isopropyl-4-methyl-2,3-dihydro-l-benzofuran-2-yl)methylcarba mate (R^ = 5.393 min,

Chiralpak AD ₅ ethanol). [α]^ ⁵ = +37.84 (c 10.0 in methanol); mp 59-62 ⁰ C; Anal, calcd. for C21H24CINO3 C ₅ 67.46; H ₅ 6.47; N ₅ 3.75. Found C ₅ 67.2; H ₅ 6.49; N, 3.58.

Intermediate 27: l-allyl-2-(benzyloxy)-3-tør/-butylbenzene Treatment of 2-allyl-6-tert-butylphenol (12.5 g, 0.066 mol) with potassium carbonate (27.24 g, 0.197 mol), benzyl bromide (11.80 g, 0.069 mol), and tetrabutylammonium iodide (2.43 g, 6.57 mmol) generally according to the procedure described for Intermediate 1 provided 16.2 g (88%) of l-allyl-2-(benzyloxy)-3-tert- butylbenzene as a colorless oil. Anal, calcd. for C20H24O: C ₅ 85.67; H, 8.63. Found: C ₅ 86.27; H ₅ 8.77.

Intermediate 28: (±)-3-[2-(benzyloxy)-3-tert-butylphenyl]propane-l,2-dioI

To a suspension of potassium ferricyanide (57.0Og ₅ 0.173 mol), potassium carbonate (24.00 g ₅ 0.174 mol), hydroquinine anthraquinone-l,4-diyl diether (0.495 g, 0.578 mmol), and potassium osmate dihydrate (0.043 g, 0.117 mmol) in wateπfert-butyl alcohol (1 :1, 600 mL) cooled to 0 ⁰ C was slowly added via an addition funnel a solution

of l-allyl-2-(benzyloxy)-3-fert-butylbenzene (16.2 g, 0.058 mol) in tert-bntyl alcohol (50 mL) and the reaction mixture was allowed to stir at 0 °C for 12 h. The reaction mixture was quenched by the addition of sodium sulfite. The reaction mixture was diluted with water (500 mL) and ethyl acetate (500 mL). The aqueous phase was separated and extracted with ethyl acetate (2 x 200 mL). The combined organic extracts were washed with saturated aqueous sodium chloride (400 mL), dried (magnesium sulfate) and the solvent was removed in vacuo to give a crude oil. Purification by flash column chromatography (silica, ethyl acetate :hexanes 3:2) gave 16.75 g (92%, 32% ee) of (±)-3- [2-(benzyloxy)-3-tert-butylphenyl]propane-l,2-diol as a white solid, mp 79-81 ⁰ C; Anal. calcd. for C20H26O3: C, 76.4; H, 8.33. Found: C, 76.39; H, 8.22.

Intermediate 29: (±)-3-(3-fer/-butyl-2-hydroxyphenyl)-2-hydroxypropyl 4- methylbenzenesulfonate

Treatment of (±)-3-[2-(benzyloxy)-3-ter/-butylphenyl]propane-l,2-diol (16.50 g, 0.053 mol) withjσ-toluenesulfonyl chloride (10.51 g, 0.055 mol) in pyridine (400 mL) generally according to the procedure described for Intermediate 3 gave 42.84 g (91%) of (±)-3-[2-(benzyloxy)-4-methoxyphenyl]-2-hydroxypropyl 4-methylbenzenesulfonate. Treatment of the tosylate with palladium on carbon (2.4 g, 10 wt.%) generally according to the procedure described for Intermediate 4 provided 14.71 g (74%) of (±)-3-(3-tert- butyl-2-hydroxyphenyl)-2-hydroxypropyl 4-methylbenzenesulfonate as a white solid, mp 98-101 ⁰ C; Anal, calcd. for C20H26O5S: C, 63.47; H, 6.92. Found: C, 63.24; H, 6.99.

Intermediate 30: (±)-(7-ter^-butyl-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate Treatment of (±)-3-(3-ført-butyl-2-hydroxyphenyl)-2-hydroxypropyl 4- methylbenzenesulfonate (14.66 g, 0.039 mol) with triphenylphosphine (11.18 g, 0.043 mol) and diethylazodicarboxylate (7.42 g, 0.043 mol) generally according to the procedure described for Intermediate 5 afforded 12.48 g (89%) of (±)-(7-tert-butyl-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate as a colorless oil. Anal. calcd. for C20H24O4S: C, 66.64; H ₅ 6.71. Found: C, 66.28; H, 6.95.

Intermediate 31: (±)-benzyl (7-fer/-butyl-2,3-dihydro-l-benzofuran-2- yl)methylcarbamate

Treatment of (±)-l-(7-tert-butyl-2,3-dihydro-l-benzofuran-2-yl)methanami ne (3.25 g, 13.4 mmol) with diisopropylethylamine (4.34 g, 33.6 mmol) and benzyl chloroformate (2.64 g, 15.5 mmol) generally according to the procedure described for Intermediate 12 gave 4.37 g (96%) of (±)-benzyl (7-tert-butyl-2,3-dihydro-l-benzofuran- 2-yl)methylcarbamate as a white solid, mp 73-76 ⁰ C; Anal. Calcd. for C21H25NO3 C,

74.31; H, 7.42; N, 4.13. Found C ₅ 74.95; H, 7.51; N ₅ 4.18. Chiral HPLC separation of (±)- benzyl (7-ført-butyl-2,3-dihydro-l-benzoforan-2-yl)methylcarbamate (Chiralcel OJ ₅ ethanol) provided two fractions. Fraction 1 (Rf = 9.100 min, Chiralcel OJ, ethanol);

Fraction 2 (R _t = 14.428 min, Chiralcel OJ ₅ ethanol).

Intermediate 32: (±)-(7-ter^-butyl-5-chloro-2,3-dihydro-l-benzofuran-2-yl)me thyl 4- methylbenzenesulfonate Treatment of 2-tert-butyl-4-chlorophenol (12.73 g ₅ 0.070 mol) with allyl bromide

(10.01 g, 0.083 mol) and potassium carbonate (38.11 g, 0.276 mol) followed by refluxing the resultant allyl ether in mesitylene generally according to the procedure described for Intermediate 8 gave 2-allyl-6-fert-butyl-4-chlorophenol. Treatment of the phenol with 3- chloroperoxybenzoic acid (35.90 g ₅ 0.146 mol, 77%) followed by potassium carbonate (28.18 g ₅ 0.204 mol) generally according to the procedure described for Intermediate 9 provided (±)-(7-tert-butyl-5-chloro-2,3-dihydro-l -benzofuran-2-yl)methanol. Treatment of the alcohol with withp-toluenesulfonyl chloride (10.27 g ₅ 0.054 mol) generally according to the procedure described for Intermediate 10 afforded 13.84 g (51%) (±)-(7- tert-butyl-5-chloro-2,3-dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate as a white solid, mp 74-77 °C; Anal, calcd. for C20H23CIO4S C ₅ 60.83; H ₅ 5.87. Found C ₅

60.79; H, 5.80.

Intermediate 33: (±)-benzyl (7-fert-butyl-5-chloro~2,3-dihydro-l-benzofuran-2- yl)methylcarbamate Treatment of (±)- 1 -(7-fert-butyl-5-chloro-2 ₅ 3-dihydro- 1 -benzofuran-2- yl)methanamine (1.80 g, 6.52 mmol) with diisopropylethylamine (2.11 g, 16.29 mmol) and benzyl chloroformate (1.28 g, 7.49 mmol) generally according to the procedure

described for Intermediate 12 gave 2.33 g (95%) of (±)-benzyl (7-tert-butyl-5-chloro-2,3~ dihydro-l-benzofuran-2-yl)methylcarbamate as a colorless oil. Anal, calcd. for C21H24CINO3 C, 67.46; H ₅ 6.47; N, 3.75. Found C, 67.27; H, 6.62; N, 3.66. Chiral

HPLC separation of (±)-benzyl (7-ført-butyl-5-chloro-2,3-dihydro-l-benzofuran-2- yl)methylcarbamate (Chiralpak AD, hexane:isopropanol 9:1) provided two fractions. Fraction 1 (R^ = 5.642 min, Chiralpak AD, hexaneasopropanol 9:1); Fraction 2 (R^ =

6.494 min, Chiralpak AD, hexane:isopropanol 9:1).

Intermediate 34: (±)-benzyl (7-fert-butyl-5-methoxy-2,3-dihydro-l-benzofuran-2- yl)methylcarbamate

Treatment of (±)-(7-fert-butyl-5-methoxy-2,3-dihydro- 1 -benzofuran-2- yl)methylamine (1.03 g, 3.8 mmol) with diisopropylethylamine (0.735 g, 5.7 mmol) and benzyl chloroformate (0.711 g, 4.2 mmol) generally according to the procedure described for Intermediate 12 gave 1.2 g (59%) of (±)-benzyl (7-tert-butyl-5-methoxy-2,3-dihydro- l-benzofuran-2-yl)methylcarbamate as a colorless oil. R/= 0.51 (silica, ethyl acetate:hexanes 2:8); Anal, calcd. for C22H27NO4 C, 71.52; H, 7.37; N, 3.79. Found C, 71.2; H, 7.44; N, 3.77.

Intermediate 35 : 2-(2~isopropylphenyl)-4,4,5,5-tetramethyl-l ,3,2-dioxaborolane To a solution of dichloro[l,l'bis(diphenylphosphino)ferrocene] palladium(II)dichloromethane adduct (0.92 g, 1.12 mmol) and 1,1 '- bis(diphenylphosphino) ferrocene (0.62 g, 1.12 mmol) in dioxane (275 mL) was added 2- isopropylphenyl trifluoromethanesulfonate (10.0 g, 37.5 mmol), bis(pinacolato)diboron (10.48 g, 41.26 mmol) and potassium acetate (10.96 g, 55.83 mmol) and the reaction mixture was heated to 90 °C and allowed to stir for 36 h. The reaction mixture was cooled to room temperature and diluted with water (300 mL) and extracted with diethyl ether (2 x 300 mL). The combined organic layers were washed with water (2 x 200 mL) and saturated aqueous sodium chloride (200 mL), were dried (magnesium sulfate), and the solvent was removed in vacuo to provide a crude oil. Purification by flash column chromatography (silica, ethyl acetate :hexane 1 :1) provided 3.9 g (43%) of 2-(2- isopropylphenyl)-4,4,5,5-tetramethyl-l,3,2-dioxaborolane as a pale yellow oil. ¹ H NMR

(DMSO-40 δ _H 7.57 (d, IH); 7.38 (t, IH); 7.30 (d, IH); 7.13 (t, IH); 3.57 (m, IH); 1.27 (s, 12H); 1.14 (d, 6H).

Intermediate 36: (±)-(4-bromo-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate

Treatment of 2-allyl-5-bromophenol (27.25 g, 0.128 mmol), with 3- chloroperoxybenzoic acid (66.20 g, 0.384 mol, 77%) ) followed by potassium carbonate (44.18 g, 0.319 mol) generally according to the procedure described for Intermediate 9 provided (±)-(4-bromo-2,3-dihydro-l-benzofuran-2-yl)methanol as a yellow oil. Treatment of the oil with/>-toluenesulfonyl chloride (15.65 g, 0.082 mol) generally according to the procedure described for Intermediate 10 afforded 24.7 g (78%) of (±)-(4- bromo-2,3-dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate as a white solid, mp 90-91 °C; Anal, calcd. for C^H ₁₅ BrO ₄ S: C, 50.14; H, 3.94. Found: C, 50.09; H,

3.82.

Intermediate 37: (±)-(4-phenyl-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate

To a solution of (±)-(4-bromo-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate (2.05 g, 5.21 mmol) and phenylboronic acid (0.952 g, 7.81 mmol) in dioxane (50 mL) heated to 100 °C was added dichlorobis(tri-o-tolylphosphine)- palladium(II) (0.205 g, 0.261 mmol) and potassium carbonate (1.80 g, 13.04 mmol) and the reaction mixture was allowed to stir at 100 °C for 12 h. The reaction mixture was cooled to room temperature, diluted with diethyl ether (250 mL), and filtered (celite). The organic layer was washed with water (2 x 100 mL) and saturated aqueous sodium chloride (100 mL), was dried (magnesium sulfate), and the solvent was removed in vacuo to provide a crude oil. Purification by flash column chromatography (silica, ethyl acetate :hexanes 1 :9) provided 1.45 g (73%) of (±)-(4-phenyl-2,3-dihydro-l-benzofuran-2~ yl)methyl 4-methylbenzenesulfonate as a clear oil. Rf= 0.34 (silica, ethyl acetate :hexanes

1:4); Anal, calcd. for C22H20O4S: C, 69.45; H, 5.30. Found: C, 69.17; H, 5.30.

Intermediate 38: (±)-benzyl (4-phenyl-2,3-dihydro-l-benzofuran-2- yl)methylcarbamate

Treatment of (±)-(4-phenyl-2,3-dihydro-l-benzofuran-2-yl)methanamine (0.622 g, 2.38 mmol) with diisopropylethylamine (0.447 g, 3.57 mmol) and benzyl chloroformate (0.462 g, 2.62 mmol) generally according to the procedure described for Intermediate 12 provided 0.601 g (70%) of (±)-benzyl (4-ρhenyl-2,3-dihydro-l-benzofuran-2- yl)methylcarbamate as a white solid, mp 132-134 ⁰ C; Anal, calcd. for C23H21NO3: C,

76.86 H ₅ 5.89; N, 3.90. Found: C, 75.98 H, 5.80; N, 3.72. Chiral HPLC separation of (±)- benzyl (4-phenyl-2,3-dihydro-l-benzofuran-2-yl)methylcarbamate (Chiralcel OD, ethanol:water 15:85) provided two fractions. Fraction 1 (R^ = 6.651 min Chiralcel OD, ethanol:water 1 :3); Fraction 2 (R^ = 7.395 min, Chiralcel OD ₃ ethanol:water 1 :3).

Intermediate 39: (±)-[4-(2-methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methy l 4- methylbenzenesulfonate Treatment of (±)-(4-bromo-2,3 -dihydro- 1 -benzofuran-2-yl)m ethyl 4- methylbenzenesulfonate (2.0 g, 5.21 mmol), 2-methylphenyl boronic acid (1.06 g, 7.82 mmol), dichlorobis(tri-o-tolylphosphine)-palladium(II) (0.205 g, 0.261 mmol), and potassium carbonate (1.80 g, 13.04 mmol) generally according to the procedure described for Intermediate 37 provided 1.41 g (69%) of (±)-[4-(2-methylphenyl)-2,3-dihydro-l- benzofuran-2-yl] methyl 4-methylbenzenesulfonate as a yellow oil. Ry= 0.42 (silica, ethyl acetate :hexanes 1:4); Anal, calcd. for C23H22O4S: C, 70.03; H, 5.62. Found: C, 69.70; H, 5.45.

Intermediate 40: (±)-benzyl [4-(2-methylphenyl)-2,3-dihydro-l-benzofuran-2- yl]methylcarbamate

Treatment of (±)-l-[4-(2-methylphenyl)-2,3-dihydro-l-benzofuran-2- yljmethanamine (0.533 g, 1.94 mmol) with diisopropylethylamine (0.375 g, 2.90 mmol) and benzyl chloroformate (0.363 g, 2.13 mmol) generally according to the procedure described for Intermediate 12 provided 0.594 g (82%) of (±)-benzyl [4-(2-methylphenyl)- 2,3 -dihydro- l-benzofuran-2-yl]methylcarbamate as colorless oil. Ry= 0.42 (silica, ethyl acetate:hexanesl:4); Anal, calcd. for C24H23NO3: C, 77.19 H, 6.21; N, 3.75. Found: C,

76.0 H, 6.01; N, 3.55. Chiral HPLC separation of (±)-benzyl [4-(2-methylphenyl)-2,3- dihydro-l-benzofuran-2-yl]methylcarbamate (Chiralcel OD, methanol) provided two fractions. Fraction 1 (R/ = 5.952 min Chiralcel OD, methanol); Fraction 2 (Rf = 7.345 min, Chiralcel OD, methanol).

Intermediate 41: l-aIlyl-2-(benzyloxy)-3-methoxybenzene

Treatment of guaiacol (25.00 g, 0.201 mol) with allyl bromide (29.24 g, 0.242 mol) and potassium carbonate (83.50 g, 0.604 mol) followed by refluxing the resultant allyl ether in mesitylene generally according to the procedure described for Intermediate 8 afforded 2-allyl-6-methoxyphenol as a brown oil. Treatment of the phenol with potassium carbonate (83.5 g, 0.604 mol), benzyl bromide (36.19 g, 0.212 mol), and tetrabutylammonium iodide (7.42 g, 0.020 mol) generally according to the procedure described for Intermediate 1 gave 23.61 g (45%) of l-allyl-2-(benzyloxy)-3- methoxybenzene as a pale yellow oil. Ry= 0.71 (silica, ethyl acetate :hexanes 1:9); Anal. calcd. for CnHi ₈ O ₂ : C, 80.28; H, 7.13. Found: C, 79.09; H, 6.93.

Intermediate 42: (±)-3-[2-(benzyIoxy)-3-methoxyphenyI]propane-l,2-diol

Treatment of (4-methoxy-l,3-benzodioxol-2-yl)methanol (23.61 g, 0.093 mol) with AD-mix-α (129.97 g) generally according to the procedure described for Intermediate 2 provided 26.49 g (99%, 34% ee) of (±)-3-[2-(benzyloxy)-3- methoxyphenyl] propane- 1,2-diol as a colorless oil. Ry= 0.63 (silica, ethyl acetate :hexanes

3:2); Anal, calcd. for C ₁₇ H ₂ OO.*: C, 70.81; H, 6.99. Found: C, 69.33; H, 7.12.

Intermediate 43: (±)-l-[2-(benzyloxy)-3-methoxyphenyl]-3-{[fert- butyl(dimethyl)silyl]oxy}propan-2-ol

To a solution of (±)-3-[2-(benzyloxy)-3-methoxyphenyl]propane- 1,2-diol (50.23 g, 0.174 mol) in N, iV-dimethylformamide (600 mL) was added tert-butyldimethylsilyl chloride (28.88 g, 0.192 mol) followed by triethylamine (22.03 g, 0.218 mol) and 4- (dimethylamino)pyridine (2.12 g, 0.017 mol) and the reaction mixture was allowed to stir at room temperature for 6 h. The reaction mixture was quenched by the addition of water (1000 mL) and was extracted with ethyl acetate (3 x 300 mL). The combined organic extracts were washed with water (4 x 300 mL), aqueous hydrogen chloride (1.0 N, 400

mL), saturated aqueous sodium chloride (300 mL), dried (magnesium sulfate) and the solvent was removed in vacuo to give a crude oil. Purification by flash column chromatography (silica, ethyl acetate :hexanes 3:7) provided 58.14 g (83%) of (±)-l-[2- (benzyloxy)-3-methoxyphenyl]-3-{[tert-butyl(dimethyl)silyl]o xy}propan-2-ol as a colorless oil. Ry= 0.48 (silica, ethyl acetate :hexanes 3:7); Anal, calcd. for C23H34U4Si:

C, 68.62; H, 8.51. Found: C, 69.20; H, 8.91.

Intermediate 44: (±)-ter^butyI[(7-methoxy-2,3-dihydro-l-benzofuran-2- yl)methoxy]dimethylsilane Treatment of (±)-l-[2-(benzyloxy)-3-methoxyphenyl]-3-{[tørt- butyl(dimethyl)silyl]oxy}propan-2-ol (58.14 g, 0.144 mol) with palladium on carbon (5.81 g, 10 wt.%) generally according to the procedure described for Intermediate 4 provided (±)-2-(3-{ [tert-butyl(dimethyl)silyl]oxy}-2-hydroxypropyl)-6-methoxyph enol as a crude oil. Treatment of the phenol with triphenylphosphine (44.52 g, 0.170 mol) and diethylazodicarboxylate (29.56 g, 0.170 mol) generally according to the procedure described for Intermediate 5 gave 34.12 g (80%) of (±)-tert-butyl[(7-methoxy-2,3- dihydro-l-benzofuran-2-yl)methoxy]dimethylsilane as a colorless oil. Ry= 0.67 (silica, ethyl acetate :hexanes 1 :9); Anal, calcd. for Ci6H26θ3Si: C, 65.26; H, 8.90. Found: C,

64.26; H, 9.24.

Intermediate 45: (±)-(7~methoxy-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate

To a solution of (±)-fer/-butyl[(7-methoxy-2,3-dihydro-l-benzofuran~2- yl)methoxy]dimethylsilane (34.12 g; 0.116 mol) in tetrahydrofuran (700 mL) cooled to 0 ⁰ C was added via an addition funnel tetrabutylammonium fluoride (140 mL, 1.0 M solution in tetrahydrofuran) and the reaction mixture was allowed to stir at room temperature for 6 h. The reaction was diluted with water (50OmL) and extracted with ethyl acetate (2 x 300 mL). The combined organic extracts were washed with saturated aqueous sodium chloride (400 mL), dried (magnesium sulfate) and the solvent was removed in vacuo to give (±)-(7-methoxy-2,3-dihydro-l-benzofuran-2-yl)methanol, a crude oil. The alcohol was dissolved in dichloromethane (700 mL) and jσ-toluenesulfonyl chloride (33.14 g, 0.174 mol) was added followed by triethylamine (21.11 g, 0.209 mol)

and then 4-(dimethylamino)pyridine (2.12 g, 0.017 mol). The reaction mixture was allowed to stir at 50 ⁰ C for 12 h. The reaction mixture was cooled to room temperature and the solvent was removed in vacuo to give a crude solid. Purification by flash column chromatography (silica, ethyl acetate:hexanes 3:7) provided 26.45 g (68%) of (±)-(7- methoxy-2,3-dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate as a white crystalline solid. Ry= 0.38 (silica, ethyl acetate :hexanes 3:7); mp 98-103 ⁰ C; Anal, calcd. for C ₁₇ HIgO ₅ S: C, 61.06; H ₅ 5.43. Found: C, 60.80; H, 5.37.

Intermediate 46: (±)-(7-hydroxy-2,3-dihydro-l-benzofuran-2~yl)methyl 4- methylbenzenesulfonate

To (±)-(7-methoxy-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate (10.00 g, 0.030 mol) was added hydrogen bromide (20 mL, 30 wt.% in acetic acid) and the resulting solution was heated to 40 ⁰ C. The reaction mixture was allowed to stir at 40 ⁰ C for 4 h. The reaction mixture was cooled to room temperature and was diluted with water (250 mL) and extracted with diethyl ether (3 x 200 mL). The combined organic extracts were washed with saturated sodium bicarbonate (3 x 300 mL), water (200 mL), and saturated aqueous sodium chloride (200 mL), were dried (magensium sulfate), and the solvent was removed in vacuo to provide a crude oil. Purification by flash column chromatography (silica, ethyl acetate :hexanes 1 :3) provided 7.34 g (77%) of (±)-(7-hydroxy-2,3-dihydro- 1 -benzofuran-2-yl)methyl 4- methylbenzenesulfonate as white solid. Ry= 0.31 (silica, ethyl acetate :hexanes 1 :3); mp

122-125 °C; Anal, calcd. for C^H ₁₆ O ₅ S: C ₃ 59.99; H, 5.03. Found: C, 59.8; H, 4.73.

Intermediate 47: (±)-(7-{[(trifluoromethyl)sulfonyI]oxy}-2,3-dihydro-l-benzo furan- 2-yl)methyl 4-methylbenzenesulfonate

Treatment of (±)-(7-hydroxy-2,3-dihydro- 1 -benzofuran-2-yl)methyl 4- methylbenzenesulfonate (1.00 g, 3.12 mmol) with diisopropylethylamine (0.44 g, 3.43 mmol) and trifluoromethanesulfonic anhydride (0.92 g, 3.28 mmol) generally according to the procedure described for Intermediate 7 gave 1.05 g (74%) of (±)-(7- { [(trifluoromethyl)sulfonyl]oxy}-2,3-dihydro-l -benzofuran-2-yl)methyl 4- methylbenzenesulfonate as a white solid. Ry= 0.45 (silica, ethyl acetate :hexanes 1 :3); mp

60-63 ⁰ C; Anal, calcd. for C ₁₇ H] ₅ F ₃ O ₇ S ₂ : C, 45.13; H, 3.34. Found: C, 44.85; H, 3.04.

Intermediate 48: (±)-(7-bromo-2,3-dihydro-l-benzofuran-2-yl)methanol

Treatment of 2-allyl-6-bromoρhenol (61.4 g 0.288 mol) with 3- chloroperoxybenzoic acid (77%, 149.18 g, 0.864 mol) ) followed by potassium carbonate (99.56 g, 0.72 mol) generally according to the procedure described for Intermediate 9 provided 49.00 g (78%) (86%) of (±)-(7-bromo-2,3-dihydro-l-benzofuran-2-yl)methanol as an amber oil. Ry= 0.66 (silica, ethyl acetate :hexanes 1:9) ¹ H NMR (DMSO-J ₆ ) δ _H 7.23

(dd, IH); 7.14 (dd, IH); 6.71 (t, IH); (5.01m, IH); 4.85 (m, IH); 4.99 (m, 2H); 3.36 (d, 2H).

Intermediate 49: (±)-(7-bromo-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate

Treatment of (±)-(7-bromo-2,3-dihydro-l-benzofuran-2-yl)methanol (49.0 g, 0.214 mol) with j?-toluenesulfonyl chloride (44.9 g, 0.235 mol) generally according to the procedure described for Intermediate 10 gave 66.00 g (80%) (±)-(7-bromo-2,3-dihydro-l- benzofuran-2-yl)methyl 4-methylbenzenesulfonate as a white solid. Ry= 0.44 (silica, ethyl acetate :hexanes 1 :4); mp 120-122 °C; Anal, calcd. for CigH^B^S: C, 50.14; H, 3.94. Found: C, 48.47; H, 4.03.

Intermediate 50: (±)-{7-[3,5-bis(trifluoromethyl)phenyl]-2,3-dihydro-l-benzo furan- 2-yI}methyl 4-methylbenzenesulfonate

To a solution of (±)-(7-{[(trifluoromethyl)sulfonyl]oxy}-2,3-dihydro-l- benzofuran-2-yl)methyl 4-methylbenzenesulfonate (1.0 g, 2.21 mmol) and 3,5- bis(trifluoromethyl)phenylboronic acid (0.86 g, 3.32 mmol) in dioxane (25 mL) heated to 90 °C was added tetrakis(triphenylphosphine)palladium(0) (0.26 g, 0.22 mmol) and potassium phosphate (0.94 g, 4.42 mmol). The reaction mixture was allowed to stir at 90 °C for 12 h. The reaction mixture was allowed to cool and was diluted with diethyl ether (100 mL), filtered (celite), and the solvent was removed in vacuo to provide a crude solid. Purification by flash column chromatography (silica, ethylacetate:hexanes 1 :9) afforded 0.75 g (66%) of (±)-{7-[3,5-bis(trifluoromethyl)phenyl]-2,3-dihydro-l-benzo furan-2- yl}methyl 4-methylbenzenesulfonate as a white solid. Ry= 0.49 (silica, ethyl acetate:hexanes 1 :3); mp 100-105 °C; Anal, calcd. for C24H18F6O4S2: C, 55.82; H,

3.51. Found: C, 55.75; H, 3.35.

Intermediate 51 : (±)-[7-(3-chloro-4-fluorophenyl)-2,3-dihydro-l-benzofuran-2 - yl] methyl 4-methylbenzenesulf onate

Treatment of (±)-(7- { [(trifluoromethyl)sulfonyl] oxy } -2,3 -dihydro- 1 -benzofuran- 2-yl)methyl 4-methylbenzenesulfonate (1.5 g, 3.32 mmol) with 3-chloro-4- fluorophenylboronic acid (0.87 g, 4.97 mmol), tetrakis(triphenylphosphine)palladium(0) (0.38 g, 0.33 mmol), and potassium phosphate (1.41 g, 6.64 mmol) generally according to the procedure described for Intermediate 50 provided 0.68 g (48%) of (±)-[7-(3-chloro-4- fluorophenyl)-2,3 -dihydro- l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate as a white solid. Ry= 0.43 (silica, ethyl acetate:hexanes 1:3); mp 104-108 °C; Anal, calcd. for

C22H18CIFO4S2: C, 61.04; H, 4.19. Found: C, 60.74; H, 4.13.

Intermediate 52: (±)-(7-phenyl-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate Treatment of (±)-(7- { [(trifluoromethyl)sulfonyl] oxy} -2,3 -dihydro- 1 -benzofuran-

2-yl)methyl 4-methylbenzenesulfonate (1.5 g, 3.32 mmol) with phenylboronic acid (0.95 g, 4.97 mmol), tetrakis(triphenylphosphine)palladium(0) (0.38 g, 0.33 mmol), and potassium phosphate (1.41 g, 6.64 mmol) generally according to the procedure described for Intermediate 50 provided 0.40 g (32%) of (±)-(7-phenyl-2,3-dihydro-l-benzofuran-2- yl)methyl 4-methylbenzenesulfonate as a white solid. Ry= 0.48 (silica, ethyl acetate:hexanes 1:3); Anal, calcd. for C ₂ 2H2θθ4S-0.2H ₂ 0: C, 68.8; H, 5.35. Found: C, 68.78; H, 5.08.

Intermediate 53: (±)-benzyl (7-phenyl-2,3-dihydro~l-benzofuran-2~ yl)methylcarbamate

Treatment of (±)-benzyl (7-phenyl-2,3-dihydro-l-benzofuran-2-yl)methanamine (1.5 g, 1.43 mmol) with diisopropylethylamine (0.277g, 2.14mmol) followed by benzyl chloroformate (0.268 g, 1.572 mmol) generally according to the procedure described for Intermediate 12 provided 1.64 (79%) of (±)-benzyl [7-ρhenyl-2,3-dihydro-l-benzofuran- 2-yl]methylcarbamate as a clear oil. Ry= 0.68 (silica, ethyl acetate :hexanes 1 :2); Anal. calcd. for C23H21NO3: C, 76.86; H, 5.89; N, 3.90. Found: C, 75.10 H, 5.71; N, 3.90.

Chiral HPLC separation of (±)-benzyl [7-phenyl-2,3-dihydro-l-benzofuran-2-

yl]methylcarbamate (Chiralpak AD, ethanol:hexane 1:1) provided two fractions. Fraction 1 (R _t = 10.746 min, Chiralpak AD, ethanol:hexane 1:1); Fraction 2 (R^ = 13.433 min, Chiralpak AD ethanol:hexane 1:1).

Intermediate 54: (±)-[7-(2-naphthyl)-2,3-dihydro-l-benzofuran-2-yl]methyl 4- methylbenzenesulfonate

Treatment of (±)-(7- { [(trifluoromethyl)sulfonyl] oxy } -2,3 -dihydro- 1 -benzofuran- 2-yl)methyl 4-methylbenzenesulfonate (1.5 g, 3.32 mmol) with 2-naphthaleneboronic acid (0.86 g, 4.97 mmol), tetrakis(triphenylphosphine)palladium(0) (0.38 g, 0.33 mmol), and potassium phosphate (1.41 g, 6.64 mmol) generally according to the procedure described for Intermediate 50 provided 0.513 g (36%) of (±)-[7-(2-naphthyl)-2,3-dihydro- l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate as a white solid. R/= 0.42 (silica, ethyl acetate :hexanes 1 :3); Anal, calcd. for C26H22O4S: C, 72.54; H, 5.15. Found: C ₅

72.04; H, 5.04.

Intermediate 55: (±)-[7-(3,5-dichIorophenyl)-2,3-dihydro-l-benzofuran-2-yl]m ethyI 4-methylbenzenesulfonate

Treatment of (±)-(7- { [(trifluoromethyl)sulfonyl] oxy} -2,3 -dihydro- 1 -benzofuran- 2-yl)methyl 4-methylbenzenesulfonate (1.5 g, 3.32 mmol) with 3,5- dichlorophenylboronic acid (0.95 g, 4.97 mmol), tetrakis(triphenylphosphine)palladium(0) (0.38 g, 0.33 mmol), and potassium phosphate (1.41 g, 6.64 mmol) generally according to the procedure described for Intermediate 50 provided 0.22 g (15%) of (±)-[7-(3,5-dichlorophenyl)-2,3-dihydro-l-benzofuran-2- yl]methyl 4-methylbenzenesulfonate as a white solid. Ry= 0.48 (silica, ethyl acetate :hexanes 1 :3); mp 113-115 °C; Anal, calcd. for C22H18CI2O4S: C, 58.8; H, 4.04. Found: C, 58.73; H, 3.77.

Intermediate 56: (±)-[7-(2-methylphenyl)-2,3-dihydro-l-benzofuran-2-y I] methyl 4- methylbenzenesulfonate Treatment of (±)-(7-bromo-2,3 -dihydro- l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate (0.50 g, 1.305 mmol) with 2-methylphenyl boronic acid (0.266 g, 1.96 mmol), dichlorobis(tri-o-tolylphosphine)-palladium(II) (0.051 g, 0.065 mmol),

and potassium carbonate (0.45 g, 3.26 mmol) generally according to the procedure described for Intermediate 37 provided 0.358 g (70%) of (±)-[7-(2-methylphenyl)-2,3- dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate as a white solid. Ry= 0.43

(silica, ethyl acetate :hexanes 1:3); mp 98-100 °C; Anal, calcd. for C23H22O4S: C, 70.03; H, 5.62. Found: C, 69.83; H, 5.61.

Intermediate 57: (±)-benzyI [7-(2-methylphenyl)-2,3~dihydro-l-benzofuran-2- yljmethylcarbamate

Treatment of (±)-[7-(2-methylphenyl)-2,3-dihydro-l-benzofuran-2- yl]methanamine (3.55 g, 12.9 mmol) with diisopropylethylamine (2.5 g, 19.4 mmol) and benzyl chloroformate (2.42 g, 14.2 mmol) generally according to the procedure described for Intermediate 12 provided 4.1 g (85%) of (±)-benzyl [7-(2-methylphenyl)-2,3-dihydro- l-benzofuran-2-yl]methylcarbamate as a clear oil 0.64 (silica, ethyl acetate :hexanes

1:4); Anal, calcd. for C24H23F4NO3: C, 77.19; H, 6.21; N, 3.75. Found: C, 76.95; H, 6.18; N, 3.53. Chiral HPLC separation of (±)-benzyl [7-(2-methylphenyl)-2,3-dihydro-l- benzofuran-2-yl]methylcarbamate (Chiralcel OD, isopropanohhexane 1 :4) provided two fractions. Fraction 1 (Rf = 7.285 min, isopropanohhexane 1:4); Fraction 2 (R^ = 9.361 min, Chiralcel OD, isopropanol:hexane 1 :4).

Intermediate 58: (±)-(7-thien-3-yl-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate

Treatment of (±)-(7-bromo-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate (0.50 g, 1.305 mmol) with 3-thiophene boronic acid (0.334 g, 2.61 mmol), dichlorobis(tri-o-tolylphosphine)-palladium(II) (0.051 g, 0.065 mmol), and potassium carbonate (0.45 g, 3.26 mmol) generally according to the procedure described for Intermediate 37 provided 0.389 g (77%) of (±)-(7-thien-3-yl-2,3-dihydro-l- benzofuran-2-yl)methyl 4-methylbenzenesulfonate as a yellow solid, mp 90-92 ⁰ C; Anal, calcd. for C2θH!8θ4S ₂ : C, 62.15; H, 4.69. Found: C, 62.2; H ₅ 4.72.

Intermediate 59: (±)-benzyl (7~thien-3-yl-2,3-dihydro-l-benzofuran-2- yl)methylcarbamate

Treatment of (±)-l-(7-thien-3-yl-2,3-dihydro-l-benzofuran-2-yl)methanami ne (0.56 g, 2.09 mmol) with diisopropylethylamine (0.406 g, 3.14 mmol) and benzyl chloroformate (0.393 g, 2.30 mmol) generally according to the procedure described for Intermediate 12 provided 0.54 g (71%) of (±)-benzyl (7-thien-3-yl-2,3-dihydro-l- benzofuran-2-yl)methylcarbamate as a colorless oil. 0.49 (silica, ethyl acetate:hexanes 2:8); Anal, calcd. for C2iHi9NO3S-0.3 H2O: C, 68.01; H, 5.33; N, 3.78.

Found: C, 67.88; H, 5.18; N, 3.72. Chiral HPLC separation of (±)-benzyl (7-thien-3-yl- 2,3-dihydro-l-benzofuran-2-yl)methylcarbamate (Chiralcel AD, water:methanol 1:9) provided two fractions. Fraction 1 (R^ = 13.00 min, (Chiralcel AD, wateπmethanol 1:9);

Fraction 2 (R^ = 14.1 min, (Chiralcel AD, watermethanol 1 :9).

Intermediate 60: (±)-[7-(2-fluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methy l 4- methylbenzenesulfonate

Treatment of (±)-(7-bromo-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate (0.50 g, 1.305 mmol) with 2-fluorophenylboronic acid (0.274 g, 1.96 mmol), dichlorobis(tri-o-tolylphosphine)-palladium(II) (0.051 g, 0.065 mmol), and potassium carbonate (0.45 g, 3.26 mmol) generally according to the procedure described for Intermediate 37 provided 0.422 g (81 %) of (±)-[7-(2-fluorophenyl)-2,3-dihydro- 1 - benzofuran-2-yl]methyl 4-methylbenzenesulfonate as a yellow solid, mp 99-101 °C; Anal, calcd. for C22H19FO4S: C, 66.32; H, 4.81. Found: C, 65.16; H, 4.86.

Intermediate 61: (±)-benzyl [7-(2~fluorophenyl)-2,3-dihydro-l-benzofuran-2- yljmethylcarbamate

Treatment of (±)-l-[7-(2-fluorophenyl)-2,3-dihydro-l-benzofuran-2- yl]methanamine (1.5 g, 5.36 mmol) with diisopropylethylamine (1.04 g, 8.04 mmol) and benzyl chloroformate (1.01 g, 5.89 mmol) generally according to the procedure described for Intermediate 12 afforded 1.7 g (84%) of (±)-benzyl [7-(2-fluorophenyl)-2,3-dihydro- l-benzofuran-2 -yljmethylcarbamate as a colorless oil Rr= 0.68 (silica, ethyl acetate:hexanes 1:9); Anal, calcd. for C22H18FNO3: C, 72.72; H, 4.99; N, 3.85. Found:

C, 72.65 H, 5.41; N, 3.47. Chiral HPLC separation of (±)-benzyl [7-(2,6- dimethylphenyl)-2,3-dihydro-l-benzoftιran-2-yl]methylcarbam ate (Chiralcel OJ, hexane:isopropanol 9:1) provided two fractions. Fraction 1 (Rγ = 13.628 min, Chiralcel

OJ, hexanedsopropanol 9:1); Fraction 2 (R^ = 17.247 min, Chiralcel OJ, hexane : isopropanol 9:1).

Intermediate 62: (±)-{7-[2-(trifluoromethyl)phenyl]-2,3-dihydro-l-benzofuran -2- yl}methyl 4-methylbenzenesulfonate

Treatment of (±)-(7-bromo-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate (10.00 g, 26.10 mmol) with 2-(trifluoromethy)phenylboronic acid (7.43 g, 39.14 mmol), dichlorobis(tri-o-tolylρhosphine)palladium(II) (0.786 g, 1.3 mmol), and potassium carbonate (9.01 g, 65.19 mmol) generally according to the procedure described for Intermediate 37 afforded 8.46 g (72%) of (±)-{7-[2- (trifluoromethyl)phenyl]-2,3-dihydro-l -benzofuran-2-yl} methyl 4- methylbenzenesulfonate as a tan solid, mp 116-118 °C; Anal, calcd. for C23H19F3O4S:

C, 61.6; H, 4.27. Found: C, 61.91; H, 4.23.

Intermediate 63: (±)-benzyl {7-[2-(trifluoromethyl)phenyl]-2,3-dihydro-l- benzofuran-2-yl}methylcarbamate Treatment of (±)-l-{7-[2-(trifluoromethyl)phenyl]-2,3-dihydro-l-benzofur an-2- yl}methanamine (0.813 g, 2.46 mmol) with diisopropylethylamine (0.478 g, 3.69 mmol) and benzyl chloroformate (0.462 g, 2.71 mmol) generally according to the procedure described for Intermediate 12 gave 0.99 g (94%) of (±)-benzyl {7-[2- (trifluoromethyl)phenyl]-2,3-dihydro-l-benzofuran-2-yl}methy lcarbamate as a pale yellow oil Ry= 0.60 (silica, ethyl acetate :hexanes 2:8); Anal, calcd. for C24H20F3NO3:

C, 67.44; H, 4.71; N, 3.15. Found: C, 67.43 H, 4.76; N, 3.15. Chiral HPLC separation of (±)-benzyl [7-(2-(trifluoromethyl))-2,3-dihydro- 1 -benzofuran-2-yl]methylcarbamate (Chiralcel OJ, isopropanol: carbon dioxide 3:17) provided two fractions. Fraction 1 (R^ =

5.252 min, Chiralcel OJ, isopropanol: carbon dioxide 3:17); Fraction 2 (R^ = 6.280 min, Chiralcel OJ, isopropanolxarbon dioxide 3:17).

Intermediate 64: (±)-[7-(2,6-dimethyIphenyl)-2,3-dihydro-l-benzofuran-2-yl]m ethyl 4-methylbenzenesulfonate

Treatment of (±)-(7-bromo-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate (1.00 g, 2.61 mmol) with 2,6-dimethylphenylboronic acid (0.783 g, 5.22 mmol), dichlorobis(tri-ø-tolylphosphine)-palladium(II) (0.103 g, 0.135 mmol), and potassium carbonate (0.90 g, 6.52 mmol) generally according to the procedure described for Intermediate 37 provided 0.192 g (18%) of (±)-[7-(2,6-dimethylρhenyl)-2,3- dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate as a yellow oil. Anal, calcd. for C24H24O4S: C, 70.56; H, 5.92. Found: C, 68.01; H ₅ 5.6.

Intermediate 65: (±)-benzyl [7-(2,6-dimethylphenyl)-2,3-dihydro-l-benzofuran-2- yl]methylcarbamate

Treatment of (±)-l-[7-(2,6-dimethylphenyl)-2,3-dihydro-l-benzofuran-2- yl]methanamine (0.947 g, 3.73 mmol) with diisopropylethylamine (0.725 g, 5.60 mmol) and benzyl chloroformate (0.7647 g, 4.48 mmol) generally according to the procedure described for Intermediate 12 gave 1.26 g (87%) of (±)-benzyl [7-(2,6-dimethylphenyl)- 2,3-dihydro-l-benzofuran-2-yl]methylcarbamate as a colorless oil R/= 0.56 (silica, ethyl acetate:hexanes 1 :4); Anal, calcd. for C25H25NO3: C, 77.49; H, 6.50; N, 3.61. Found: C,

77.42 H, 6.57; N, 3.62. Chiral HPLC separation of (±)-benzyl [7-(2,6-dimethylphenyl)- 2,3-dihydro-l-benzofuran-2-yl]methylcarbamate (Chiralcel OJ, methanol: carbon dioxide 4:6) provided two fractions. Fraction 1 (R^ = 2.89 min, Chiralcel OJ, methanol: carbon dioxide 4:6); Fraction 2 (R^ = 3.84 min, Chiralcel OJ, methanol: carbon dioxide 4:6).

Intermediate 66: (±)-[7-(2-methoxyphenyl)-2,3-dihydro-l-benzofuran-2-yI]meth yl 4- methylbenzenesulfonate

Treatment of (±)-(7-bromo-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate (0.5 g, 1.31 mmol) with 2-methoxyphenylboronic acid (0.297 g, 1.96 mmol), dichlorobis(tri-o-tolylphosphine)palladium(II) (0.051 g, 0.065 mmol), and potassium carbonate (0.45 g, 3.26 mmol) generally according to the procedure described for Intermediate 37 gave 0.399 g (74%) of (±)-[7-(2-methoxyphenyl)-2,3-dihydro-l- benzofuran-2-yl] methyl 4-methylbenzenesulfonate as a tan solid, mp 100-103 ⁰ C; Anal. calcd. for C23H22O5S: C, 67.3; H, 5.4. Found: C, 66.95; H, 5.43.

Intermediate 67: (±)-benzyI [7-(2-methoxyphenyl)-2,3-dihydro-l-benzofuran-2- yl]methylcarbamate

Treatment of (±)-l-[7-(2-methoxyphenyl)-2,3-dihydro-l-benzofuran-2- yl]methanamine (0.296 g, 1.01 mmol) with diisopropylethylamine (1.52 g, 1.5 mmol) and benzyl chloroformate (0.190 g, 1.11 mmol) generally according to the procedure described for Intermediate 12 afforded 0.33 g (84%) (±)-benzyl [7-(2-methoxyρhenyl)- 2,3-dihydro-l-benzofuran-2-yl]methylcarbamate of a colorless oil Ry= 0.72 (silica, ethyl acetate:hexanes 2:8); Anal, calcd. for C24H23NO4: C, 74.02; H, 5.95; N, 3.6. Found: C, 73.68 H, 5.81; N, 3.43.

Intermediate 68: (±)-[7-(2-chlorophenyl)-2,3-dihydro-l-benzofuran-2-yl] methyl 4- methylbenzenesulfonate

Treatment of (±)-(7-bromo-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate (0.50 g, 1.305 mmol)with 2-chlorophenylboronic acid (0.306 g, 1.96 mmol), dichlorobis(tri-o-tolylphosphine)-palladium(II) (0.051 g, 0.065 mmol), and potassium carbonate (0.45 g, 3.26 mmol) generally according to the procedure described for Intermediate 37 provided 0.380 g (70%) of (±)-[7-(2-chlorophenyl)-2,3-dihydro-l- benzofuran-2-yl] methyl 4-methylbenzenesulfonate as a tan solid, mp 100-103 °C; Anal. calcd. for C22H19CIO4S: C, 63.69; H, 4.62. Found: C, 63.43; H, 4.69.

Intermediate 69: (±)-benzyl [7-(2-chlorophenyl)-2,3-dihydro-l-benzofuran-2- yljmethylcarbamate

Treatment of (±)~ 1 - [7-(2-chlorophenyl)-2,3 -dihydro- 1 -benzofuran-2- yl]methanamine (0.743 g 2.52 mmol) with diisopropylethylamine (0.488 g, 3.77 mmol) and benzyl chloroformate (0.472 g, 2.77 mmol) generally according to the procedure described for Intermediate 12 afforded 0.749 g (76%) (±)-benzyl [7-(2-chlorophenyl)-2,3- dihydro-l-benzofuran-2-yl]methylcarbamate as a white solid, mp 155-157 ⁰ C; Anal, calcd. for C23H20CINO3: C, 70.14; H, 5.12; N, 3.56. Found: C, 70.1; H, 5.15; N, 3.37. Chiral HPLC separation of (±)-benzyl [7-(2-chlorophenyl)-2,3-dihydro-l-benzofuran-2- yl]methylcarbamate (Chiralcel OJ ₅ hexane:ethanol 1 :1) provided two fractions. Fraction 1

(R _t = 9.655 min, Chiralcel OJ, hexane:ethanol 1 :1); Fraction 2 (R^ = 16.300 min, Chiralcel OJ, hexane:ethanol 1:1).

Intermediate 70: (±)-benzyl [7-(2-isopropylphenyl)-2,3-dihydro-l~benzofuran-2- yljmethylcarbamate

Treatment of (±)-[7-(2-isopropylphenyl)-2,3-dihydro- 1 -benzofuran-2- yl]methylamine (1.69 g, 5.56 mmol) with diisopropylethylamine (1.08 g, 8.34 mmol) and benzyl chloroformate (1.04 g, 6.12 mmol) generally according to the procedure described for Intermediate 12 gave 1.92 (89%) of (±)-benzyl [7-(2-isoρroρylρhenyl)-2,3-dihydro-l- benzofuran-2-yl]methylcarbamate as a yellow oil. Ry= 0.66 (silica, ethyl acetate :hexanes

1:4); Anal, calcd. for C26H27NO3: C, 77.78; H, 6.78; N, 3.49. Found: C, 77.5; H, 6.7; N, 3.33. Chiral HPLC separation of (±)-[7-(2-isopropylphenyl)-2,3-dihydro-l-benzofuran-2- yl]methylcarbamate (Chiralcel OD, hexane:isopropanol 9:1) provided two fractions. Fraction 1 (R^ = 8.131 min, Chiralcel OD, hexane:isopropanol 9:1); Fraction 2 (R^ = 11.048 min, Chiralcel OD, hexane:isopropanol 9:1).

Intermediate 71: (±)-[7-(3-methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methy l 4- methylbenzenesulfonate

Treatment of (±)-(7- { [(trifluoromethyl)sulfonyl] oxy } -2,3 -dihydro- 1 -benzofuran- 2-yl)methyl 4-methylbenzenesulfonate (1.5 g, 3.32 mmol) with 3-methylbenzeneboronic (0.68 g, 4.97 mmol), tetrakis(triphenylphosphine)palladium(0) (0.38 g, 0.33 mmol), and potassium phosphate (1.41 g, 6.64 mmol) generally according to the procedure described for Intermediate 50 provided 0.899 g (69%) of (±)-[7-(3-methylphenyl)-2,3-dihydro-l- benzofuran-2-yl] methyl 4-methylbenzenesulfonate as a white solid. Ry= 0.44 (silica, ethyl acetate :hexanes 1:3); mp 81-82 ⁰ C; Anal, calcd. for C23H22C\4S-0.2H2θ: C, 69.39; H, 5.67. Found: C ₃ 69.42; H, 5.49.

Intermediate 72: (±)-benzyl [7-(3~methyIphenyI)-2,3-dihydro-l-benzofuran-2- yljmethylcarbamate Treatment of (±)-[7-(3-methylphenyl)-2,3-dihydro-l-benzofuran-2- yl]methanamine (1.76 g, 6.38 mmol) with diisopropylethylamine (2.47 g, 19.17mmol) followed by benzyl chloroformate (1.19 g, 7.02 mmol) generally according to the

procedure described for Intermediate 12 provided 1.4 g (58%) of (±)-benzyl [7-(3- methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methylcarbamate as a clear oil. Ry= 0.68

(silica, ethyl acetate:hexanes 1:2); Anal, calcd. for C24H23NO3: C, 77.19; H, 6.20; N,

3.75. Found: C, 76.88 H, 6.25; N, 3.51. Chiral HPLC separation of (±)-benzyl [7-(3- methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methylcarbamate (Chiralpak AD, ethanohhexane 1:1) provided two fractions. Fraction 1 (R^ = 10.439 min, Chiralpak AD ₅ ethanol:hexane 1 :1); Fraction 2 (R^ = 11.833 min, Chiralpak AD ethanol:hexane 1:1).

Intermediate 73: (±)-[7-(3-fluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methy l 4- methylbenzenesulfonate

Treatment of (±)-(7-bromo-2,3-dihydro-l-benzofuran-2-yl)m ethyl 4- methylbenzenesulfonate (0.50 g, 1.305 mmol) with 3-fluorophenylboronic acid (0.274 g, 1.96 mmol), dichlorobis(tri-o-tolylphosphine)-palladium(II) (0.051 g, 0.065 mmol), and potassium carbonate (0.45 g, 3.26 mmol) generally according to the procedure described for Intermediate 37 provided 0.392 g (75%) of (±)-[7-(3-fluorophenyl)-2,3-dihydro-l- benzofuran-2-yl] methyl 4-methylbenzenesulfonate as a light yellow solid, mp 88-90 °C; Anal, calcd. for C22H19FO4S: C, 66.32; H, 4.81. Found: C, 65.63; H, 4.84.

Intermediate 74: (±)-benzyl [7-(3-fluorophenyl)-2,3-dihydro-l-benzofuran-2- yljmethylcarbamate

Treatment of (±)-[7-(3-fluorophenyl)-2,3-dihydro-l-benzofuran-2- yl]methanamine (0.798 g, 2.856 mmol) with diisopropylethylamine (0.554 g, 4.286 mmol) and benzyl chloroformate (0.536 g, 3.143 mmol) generally according to the procedure described for Intermediate 12 afforded 1.01 g (94%) of (±)-benzyl [7-(3- fluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methylcarbamate as a white solid. 0.40

(silica, ethyl acetate :hexanes 1:4); Anal. Calcd. for C23H20FNO3: C, 73.2; H, 5.34; N, 3.71. Found: C, 92.96; H, 5.38; N, 3.59.

Intermediate 75: (±)-[7-(3-chlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methy l 4- methylbenzenesulfonate

Treatment of (±)-(7-bromo-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate (0.50 g, 1.305 mmol) with 3-chlorophenylboronic acid (0.306 g, 1.96 mmol), dichlorobis(tri-o-tolylphosphine)-palladium(II) (0.051 g, 0.065 mmol), and potassium carbonate (0.45 g, 3.26 mmol) generally according to the procedure described for Intermediate 37 provided 0.404 g (75%) of (±)-[7-(3-chlorophenyl)-2,3-dihydro-l- benzofuran-2-yl] methyl 4-methylbenzenesulfonate as a light yellow solid, mp 101-103 °C; Anal, calcd. for C22H19CIO4S: C, 63.69; H, 4.62. Found: C, 63.59; H, 4.52.

Intermediate 76: (±)-benzyl [7-(3-chlorophenyl)-2,3-dihydro-l-benzofuran-2- yl]methylcarbamate

Treatment of (±)-l-[7-(3-chlorophenyl)-2,3-dihydro-l-benzofuran-2- yl]methanamine (1.6 g, 5.4 mmol) with diisopropylethylamine (1.197 g, 9.26 mmol) and benzyl chloroformate (1.02 g, 5.96 mmol) generally according to the procedure described for Intermediate 12 afforded 1.59 g (75%) of (±)-benzyl [7-(3-chlorophenyl)-2,3-dihydro~ l-benzofuran-2-yl]methylcarbamate as a colorless oil. Ry= 0.56 (silica, ethyl acetate:hexanes 1 :9); Anal, calcd. for C23H20CINO3: C, 70.14; H ₅ 5.12; N, 3.56. Found:

C, 69.11; H, 5.07; N, 3.37. Chiral HPLC separation of (±)-benzyl [7-(3-chlorophenyl)- 2,3-dihydro-l-benzofuran-2-yl]methylcarbamate (Chiralcel OD, hexanedsopropanol 9:1) provided two fractions. Fraction 1 (R^ = 15.935 min Chiralcel OD, hexane:isopropanol 9:1); Fraction 2 (R^ = 18.546 min, Chiralcel OD, hexanedsopropanol 9:1).

Intermediate 77: (±)-[7-(3-methoxyphenyl)-2,3-dmydro-l-benzofuran-2-yl]methy I 4- methylbenzenesulfonate

Treatment of (±)-(7-bromo-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate (5.00 g, 13.04 mmol) with 3-methoxyphenylboronic acid (2.97 g, 19.57 mmol), dichlorobis(tri-o-tolylphosphine)palladium(II) (0.512 g, 0.652 mmol) and potassium carbonate (4.51 g, 32.62 mmol) generally according to the reaction conditions described for Intermediate 37 gave 4.48 g (84%) of (±)-[7-(3-methoxyphenyl)-2,3~ dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate as a white solid, mp 141-

142 ⁰ C; Anal, calcd. for C23H22O5S: C, 67.3; H, 5.4. Found: C, 66.51; H, 5.41.

Intermediate 78: (±)-benzyl [7-(3-methoxyphenyl)-2,3-dihydro-l-benzofuran-2- y 1] methylcarb amate

Treatment of (±)-l-[7-(3-methoxyphenyl)-2,3-dihydro-l-benzofuran-2- yl]methanamine (2.4 g, 9.4 mmol) with diisopropylethylamine (1.82 g, 14.10 mmol) and benzyl chloroformate (1.92 g, 11.28 mmol) generally according to the reaction conditions described for Intermediate 12 afforded 3.42 g (93%) of (±)-benzyl [7-(3-methoxyphenyl)-

2,3-dihydro-l-benzofuran-2-yl]methylcarbamate as a colorless oil. Ry= 0.78 (silica, ethyl acetate:hexanes 1:4); Anal, calcd. for C24H23NC-4-: C, 74.02; H, 5.95; N, 3.6. Found: C, 73.52; H, 6.06; N, 3.28.

Intermediate 79: (±)-{7-[3-(trifluoromethyl)phenyl]-2,3-dihydro-l-benzofuran -2- yl}methyl 4-methylbenzenesulfonate

Treatment of (±)-(7-bromo-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate (0.50 g, 1.305 mmol) with 3-(trifluoromethyl)phenylboronic acid (0.372 g, 1.96 mmol), dichlorobis(tri-o-tolylphosphine)-palladium(II) (0.051 g, 0.065 mmol), and potassium carbonate (0.45 g, 3.26 mmol) generally according to the procedure described for Intermediate 37 provided 0.383 g (65%) of (±)-{7-[3- (trifluoromethyl)phenyl]-2,3-dihydro-l-benzofuran-2-yl}methy l 4- methylbenzenesulfonate as a white solid, mp 90-93 °C; Anal, calcd. for C23H19F3O4S:

C, 61.6; H, 4.27. Found: C, 61.52; H, 4.21.

Intermediate 80: (±)-benzyl {7-[3~(trifluoromethyl)phenyl]-2,3-dihydro-l- benzofuran-2-yl}methylcarbamate Treatment of (±)-[7-(3-trifluoromethylphenyl)-2,3-dihydro-l-benzofuran-2 - yl]methanamine (1.67 g, 5.06 mmol) with diisopropylethylamine (0.98 g, 7.59 mmol) and benzyl chloroformate (1.04 g, 6.07 mmol) generally according to the procedure described for Intermediate 12 provided 2.1 g (97%) of (±)-benzyl {7-[3-(trifluoromethyl)phenyl]- 2,3-dihydro-l-benzofuran-2-yl}methylcarbamate as a colorless oil. Ry= 0.51; Anal. calcd. for C24H20F3NO3: C, 67.44; H, 4.72; N, 3.28. Found: C, 67.08; H, 5.05; N, 3.22.

Intermediate 81: (±)-[7-(4-methylphenyl)-2,3-dihydro-l-benzofuran-2-yI]methy l 4- methylbenzenesulfonate

Treatment of (±)-(7-bromo-2,3-dihydro-l-benzofuran-2-yl)methyl A- methylbenzenesulfonate (11.2 g, 29.22 mmol) with 4-methylphenylboronic acid (5.96 g, 43.84 mmol), dichlorobis(tri-o-tolylphosphine)-palladium(II) ( 1.148 g, 1.46 mmol), and potassium carbonate (10.10 g, 73.07 mmol) generally according to the procedure described for Intermediate 37 afforded 9.8 g (85%) of (±)-[7-(4-methylρhenyl)-2,3- dihydro-l-benzofuran-2-yl] methyl 4-methylbenzenesulfonate a white solid, mp 145-147 ⁰ C; Anal, calcd. for C23H22O4S: C, 70.03; H ₅ 5.62. Found: C, 69.91; H, 5.70.

Intermediate 82: (±)-benzyl [7-(4-methylphenyl)-2,3-dihydro-l-benzofuran-2- yl]methylcarbamate

Treatment of (±)-[7-(4-methylphenyl)-2,3-dihydro-l-benzofuran-2- yl]methanamine (0.385 g, 1.396 mmol) with diisopropylethylamine (0.270 g, 2.09 mmol) and benzyl chloro formate (0.285 g, 1.675 mmol) generally according to the procedure described for Intermediate 12 provided 0.483 g (93%) of (±)-benzyl [7-(4-methylphenyl)- 2,3-dihydro-l-benzofuran-2-yl]methylcarbamate as colorless oil. 0.47 (silica, ethyl acetate :hexane 2:8); mp 83-86 ⁰ C; Anal, calcd. for C24H23NO3: C, 77.19; H, 6.21; N,

3.75. Found: C, 76.97; H, 5.99; N, 3.68. Chiral HPLC separation of (±)-benzyl [7-(4- methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methylcarbamate (Chiralpak OD, methanol: carbon dioxide 1:1) provided two fractions. Fraction 1 (R^ = 3.788 min

Chiralpak OD, methanol:carbon dioxide 1:1); Fraction 2 (R^ = 4.398 min, Chiralpak OD, methanol: carbon dioxide 1 :1).

Intermediate 83: (±)-[7-(4-methoxyphenyl)-2,3-dihydro-l-benzofuran-2-yl]meth yl 4- methylbenzenesulfonate

Treatment of (±)-(7-bromo-2,3-dihydro-l-benzofuran-2-yl)methyl A- methylbenzenesulfonate (3.0 g, 7.82 mmol) with 4-methoxyphenylboronic acid (1.78 g, 11.74 mmol), dichlorobis(tri-o-tolylphosphine)-palladium(II) (0.307 g, 0.391 mmol), and potassium carbonate (2.70 g, 19.57 mmol) generally according to the procedure described for Intermediate 37 provided 2.2 g (68%) of (±)-[7-(4-methoxyphenyl)-2,3-dihydro-l-

benzofuran-2-yl]methyl 4-methylbenzenesulfonate as a yellow solid, mp 116-117 ⁰ C; Anal, calcd. for C23H22O5S: C, 67.30; H, 5.40. Found: C, 67.31; H ₅ 5.35.

Intermediate 84: (±)-benzyl [7~(4-methoxypkenyl)-2,3-dihydro~l-benzofuran~2- yljmethylcarbamate

Treatment of l-[7-(4-methoxyphenyl)-2,3-dihydro-l-benzofuran-2- yl]methanamine (0.727 g, 2.49 mmol) with diisopropylethylamine (0.483 g, 3.73) and benzyl chloroformate (0.510 g, 2.99 mmol) generally according to the procedure described for Intermediate 12 provided 0.820 g of (±)-benzyl [7-(4-methoxyphenyl)-2,3- dihydro-l-benzofuran-2-yl]methylcarbamate as a colorless oil. Ry"= 0.48 (silica, ethyl acetate:hexanes 1:5); Anal, calcd. for C24H23NO4: C, 74.02; H, 5.95; N, 3.60. Found: C,

73.66 H, 6.13; N, 3.42. Chiral HPLC separation of (±)-benzyl [7-(4-methoxyphenyl)-2,3- dihydro-l-benzofuran-2-yl]methylcarbamate (Chiralcel AD, methanol) provided two fractions. Fraction 1 (R^ = 7.386 min, Chiralcel AD, methanol); Fraction 2 (R^ = 10.882 min, Chiralcel AD, methanol).

Intermediate 85: (±)-{7-[4-(trifluoromethyl)phenyl]-2,3-dihydro-l-benzofuran -2- yl}methyl 4-methylbenzenesulfonate

Treatment of (±)-(7-bromo-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate (0.50 g, 1.305 mmol) with 4-(trifluoromethyl)phenylboronic acid (0.372 g, 1.96 mmol), dichlorobis(tri-o-tolylphosphine)-palladium(II) (0.051 g, 0.065 mmol), and potassium carbonate (0.45 g, 3.26 mmol) generally according to the procedure described for Intermediate 37 provided 0.435 g (74%) of (±)-{7~[4- (trifluoromethyl)phenyl]-2,3-dihydro-l-benzofuran-2-yl}methy l 4- methylbenzenesulfonate as a light yellow solid, mp 116-118 °C; Anal, calcd. for C23H19F3O4S: C, 61.6; H, 4.27. Found: C, 61.37; H, 4.36.

Intermediate 86: (±)-benzyl {7-[4-(trifluoromethyl)phenyl]-2,3-dihydro-l- benzofuran-2-yl}methylcarbamate Treatment of (±)-l-{7-[4-(trifluoromethyl)phenyl]-2,3-dihydro-l-benzofur an-2- yl}methanamine (1.8 g, 6.14 mmol) with diisopropylethylamine (1.06 g, 8.20) and benzyl chloroformate (1.12 g, 6.56 mmol) generally according to the procedure described for

Intermediate 12 afforded 2.38 g (91%) of (±)-benzyl {7-[4-(trifluoromethyl)phenyl]-2,3- dihydro-l-benzofuran-2-yl}methylcarbamate as a white solid. Rr= 0.48 (silica, ethyl acetate:hexanes 1 :4); mp 100-102 °C; Anal, calcd. for C24H20F3NO3: C, 67.44; H, 4.72;

N ₅ 3.28. Found: C, 67.37; H, 4.69; N ₅ 3.15.

Intermediate 87: (±)-[7-(4-fluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methy l 4- methylbenzenesulfonate

Treatment of (±)-(7-bromo-2,3-dihydro-l-benzofuran-2-yl)methyl A- methylbenzenesulfonate (0.50 g, 1.305 mmol) with 4-fluorophenylboronic acid (0.274 g, 1.96 mmol), dichlorobis(tri-o-tolylphosphine)-palladium(II) (0.051 g, 0.065 mmol), and potassium carbonate (0.45 g, 3.26 mmol) generally according to the procedure described for Intermediate 37 provided 0.408 g (78%) of (±)-[7-(4-fluorophenyl)-2,3-dihydro-l- benzofuran-2-yl]methyl 4-methylbenzenesulfonate as a light yellow solid, mp 83-86 ⁰ C; Anal, calcd. for C22H19FO4S: C, 66.32; H, 4.81. Found: C, 66.11; H, 4.61.

Intermediate 88: (±)-[7-(4-chIorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methy l 4- methylbenzenesulfonate

Treatment of (±)-(7-bromo-2,3-dihydro-l-benzofuran-2-yl)methyl A- methylbenzenesulfonate (0.50 g, 1.305 mmol) with 4-chlorophenylboronic acid (0.306 g, 1.96 mmol), dichlorobis(tri-o-tolylphosphine)-palladium(II) (0.051 g, 0.065 mmol), and potassium carbonate (0.45 g, 3.26 mmol) generally according to the procedure described for Intermediate 37 provided 0.367 g (68%) of (±)-[7-(4-chlorophenyl)-2,3-dihydro-l- benzofuran-2-yl] methyl 4-methylbenzenesulfonate as an orange solid, mp 130-133 °C; Anal, calcd. for C22H19CIO4S: C ₅ 63.69; H, 4.62. Found: C ₅ 62.82; H, 4.56.

Intermediate 89: (±)-[7-(2,4-dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]m ethyl 4-methylbenzenesulfonate

Treatment of (±)-(7-bromo-2,3-dihydro-l-benzofuran-2-yl)methyl A- methylbenzenesulfonate (5.0 g, 13.05 mmol) with 2,4-dichlorophenylboronic acid (3.73 g, 19.57 mmol), dichlorobis(tri-o-tolylphosphine)-palladium(II) (0.512 g, 0.652 mmol), and potassium carbonate (4.51 g, 32.62 mmol) generally according to the procedure described for Intermediate 37 provided 4.5 g (75%) of (±)-[7-(2,4-dichlorophenyl)-2,3-

dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate as a yellow oil. Anal, calcd. for C22H18CI2O4S: C, 58.8; H, 4.04. Found: C, 59.01; H, 4.09.

Intermediate 90: (±)-benzyl [7-(2,4-dichlorophenyl)-2,3-dihydro-l-benzofuran-2- yl]methylcarbamate

Treatment of (±)-l-[7-(2,4-dichlorophenyl)-2,3-dihydro-l-benzofuran-2- yl]methanamine (1.9 g, 5.75 mmol) with diisopropylethylamine (1.11 g, 8.62) and benzyl chloroformate (1.18 g, 6.89 mmol) generally according to the procedure described for Intermediate 12 afforded 2.14 g (87%) of (±)-benzyl [7-(2,4-dichlorophenyl)-2,3-dihydro- l-benzofuran-2-yl]methylcarbamate as a white solid, mp 87-89 °C; Anal, calcd. for C23H19CI2NO3: C, 64.5; H, 4.47; N, 3.27. Found: C, 64.65; H, 4.78; N, 3.08.

Intermediate 91: (±)-3-[2-(benzyloxy)-5-chloro-3-methoxyphenyl]propane-l,2-d ioI

Treatment of 4-chloro-2-methoxyphenol (30.0 g, 0.19 mol) with sodium hydride (9.1 g, 0.23 mol, 60 wt.%) and allyl bromide (27.46 g, 0.23 mol) followed by treatment of the resultant allyl ether in refluxing mesitylene generally according to the procedure described for Intermediate 8 gave 2-allyl-4-chloro-6-methoxyphenol as a yellow oil. Treatment of 2-allyl-4-chloro-6-methoxyphenol with sodium hydride (7.08 g, 0.177 mol, 60 wt.%) and benzyl bromide (30.27 g, 0.177 mol) generally according to the procedure described for Intermediate 13 provided l-allyl-2-(benzyloxy)-5-chloro-3- methoxybenzene as a pale yellow oil. Treatment of the olefin (35.5 g, 0.123 mol) of with AD-mix-α (132.0 g) generally according to the procedure described for Intermediate 2 gave 35 g (54%) of (±)-3-[2-(benzyloxy)-5-chloro-3-methoxyphenyl]propane-l,2-d iol as a white solid, mp. 65-68 ⁰ C. Anal, calcd. for C17H19CIO4: C, 63.26; H, 5.93. Found: C, 65.29; H, 6.23.

Intermediate 92: (±)-(5-chloro-7-methoxy-2,3-dihydro-l-benzofuran-2-yI)methy l 4- methylbenzenesulfonate

Treatment of (±)-3-[2-(benzyloxy)-5-chloro-3-methoxyphenyl]-l ,2-propanediol (32 g, 0.1 mol) with/?-toluenesulfonyl chloride (21 g, 0.11 mol) in pyridine generally according to the procedure described for intermediate 3 provided (±)-3-[2-(benzyloxy)-5- chloro-3-methoxyphenyl]-2-hydroxypropyl 4-methylbenzenesulfonate. Treatment of the

tosylate with palladium on carbon (2.32 g, 5 wt.%) generally according to the procedure described for Intermediate 4 afforded (±)-3-(5-chloro-2-hydroxy-3-methoxyphenyl)-2- hydroxypropyl 4-methylbenzenesulfonate. Treatment of the phenol with triphenylphosphine (23.6 g, 0.09 mol) and diisopropyl azodicarboxylate (18.2 g, 0.09 mol) generally according to the procedure described for Intermediate 5 afforded 28 g (76%) of (±)-(5-chloro-7-methoxy-2,3-dihydro-l-benzofuran-2-yl)methy l A- methylbenzenesulfonate as a pale yellow solid, mp 99-102 ⁰ C; Anal, calcd. for C17H17CIO5S: C, 55.36; H, 4.65. Found: C, 55.35; H, 4.62.

Intermediate 93: (±)-(5-chloro-7-{[(trifluoromethyl)suIfonyl]oxy}-2,3-dihydr o-l- benzofuran-2-yl)methyl 4-methylbenzenesuIfonate

Treatment of (±)-(5-chloro-7~methoxy-2,3-dihydro-l -benzofuran-2-yl)methyl A- methylbenzenesulfonate (22.1 g, 0.06 mol) with hydrogen bromide (400 mL, 30 wt.% in acetic acid) generally according to the procedure described for Intermediate 46 gave 14.6 g of (±)-(5-chloro-7-hydroxy-2,3-dihydro-l-benzofuran-2-yl)methy l 4- methylbenzenesulfonate as a colorless oil. Treatment of (±)~(5-chloro-7-hydroxy-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (4.5 g, 12.68 mmol) with trifluoromethanesulfonic anhydride (2.34 mL, 13.9 mmol) and diisopropylethylamine (2.43 mL, 13.9 mmol) generally according to the procedure described for Intermediate 7 provided 6.27 g (99%) of (±)-(5-chloro-7-{ [(trifluoromethyl)sulfonyl]oxy} -2,3-dihydro- l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate as a light yellow solid, mp 55-57 °C; Anal, calcd. for Ci ₇ Hi ₄ ClF ₃ O ₇ S ₂ : C, 41.94; H, 2.90. Found: C, 42.10; H, 2.76.

Intermediate 94: (±)-(5-chIoro-7-phenyI-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate

Treatment of (±)-(5-chloro-7- { [(trifluoromethyl)sulfonyl]oxy} -2,3-dihydro- 1 - benzofuran-2-yl)methyl 4-methylbenzenesulfonate (1.50 g, 3.10 mmol) with phenyl boronic acid (0.564 g, 4.60mmol), dichloro[l,l '- bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (0.252 g, 0.30 mmol), and potassium carbonate (0.829 g, 6.0 mmol) generally according to the procedure described for Intermediate 35 provided 0.94 g of a white paste. Re- crystallization from methanol afforded 0.6 g (47%) of (±)-(5-chloro-7-phenyl-2,3-

dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate as a white solid, mp 127- 130 °C; Anal, calcd. for C22H ₁₉ Clθ4S: C, 63.69; H, 4.62. Found: C, 62.51; H, 4.48.

Intermediate 95: (±)-[5-chloro-7-(3-chIorophenyl)-2,3-dihydro-l-benzofuran-2 - yl]methyl 4-methylbenzenesulfonate

Treatment of (±)-(5 -chloro-7- { [(trifluoromethyl)sulfonyl] oxy } -2,3-dihydro- 1 - benzofuran-2-yl)methyl 4-methylbenzenesulfonate (1.5O g, 3.10 mmol) with 3- chlorophenylboronic acid (0.72 g, 4.60 mmol), dichloro[l,l'- bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (0.252 g, 0.30 mmol), and potassium carbonate (0.829 g, 6.0 mmol) generally according to the procedure described for Intermediate 35 gave 1.1 g (80%) of (±)-[5-chloro-7-(3- chlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate as a white solid, mp 80-82 °C. Anal, calcd. for C22H18CI2O4S: C, 58.8; H, 4.04. Found: C,

56.91; H ₅ 3.82.

Intermediate 96: (±)-(5-chloro-7-thien-3-yl-2,3-dihydro-l-benzofuran-2-yl)me thyl 4- methylbenzenesulfonate

Treatment of (±)-(5 -chloro-7- { [(trifluoromethyl)sulfonyl] oxy} -2,3-dihydro- 1 - benzofuran-2-yl)methyl 4-methylbenzenesulfonate (1.50 g, 3.10 mmol) with thiophene-3- boronic acid (0.62 g, 4.88 mmol), dichloro[l,l '- bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (0.265 g, 0.325 mmol), and potassium carbonate (0.898 g, 6.5 mmol) generally according to the procedure described for Intermediate 35 provided 0.22 g (17%) of (±)-(5-chloro-7-thien- 3-yl-2,3-dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate as a white solid. mp 115-117 °C; Anal, calcd. for C20H17CIO4S2: C ₅ 57.07; H, 4.07. Found: C ₅ 56.17; H ₅ 3.85.

Intermediate 97: (±)-2-(azidomethyl)-5-chloro-7-(3-methylphenyl)-2,3-dihydro -l- benzofuran Treatment of (±)-(5-chloro-7-{[(trifluoromethyl)sulfonyl]oxy}-2,3-dihydr o-l- benzofuran-2-yl)methyl 4-methylbenzenesulfonate (1.50 g, 3.10 mmol) with 3- methylphenylboronic acid (0.63 g ₅ 4.60 mmol), dichloro[l,l'-

bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (0.252 g, 0.30 mmol), and potassium carbonate (0.829 g, 6.0 mmol) generally according to the procedure described for Intermediate 35 gave (±)-[5-chloro-7-(3-methylphenyl)-2,3- dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate as a colorless oil. Treatment of the tosylate with sodium azide (0.31 g, 4.78 mmol) generally according to the procedure described for Intermediate 98 afforded 0.32 g (34%) of (±)-2- (azidomethyl)-5-chloro-7-(3-methylphenyl)-2,3-dihydro-l-benz ofuran as a tan solid, mp 48-50 °C; Anal, calcd. for Ci ₆ H ₁₄ ClNsO: C, 64.11; H.4.71; N, 14.02. Found: C, 62.95;

H, 4.62; N, 13.72.

Intermediate 98: (±)-2-(azidomethyI)-5-chloro-7-thien-3-yl-2,3-dihydro-l- benzofuran

To a solution of (±)-(5-chloro-7-thien-3-yl-2,3-dihydro-l-benzofuran-2-yl)me thyl 4-methylbenzenesulfonate (4.5 g, 10.69 mmol) in dimethylsulf oxide (150 mL) was added sodium azide (3.6 g, 55.38 mmol) and the reaction mixture was heated to 70 ⁰ C and allowed to stir for 6 h. The reaction mixture was cooled to room temperature and diluted with water (300 mL) and diethyl ether (200 mL). The aqueous layer was separated and extracted with diethyl ether (200 mL). The combined organic layers were washed with water (3 x 200 mL), saturated aqueous sodium chloride (100 mL), dried (magnesium sulfate), and the solvent removed in vacuo to afford 2.6 g (83%) of (±)-2-(azidomethyl)- 5-chloro-7-thien-3-yl-2,3-dihydro-l-benzofuran as a white solid, mp 50-52 °C; Anal, calcd. for C ₁₃ Hi ₀ ClN3θS: C, 53.52; H, 3.45; N, 14.40. Found: C, 53.50; H, 3.33; N,

14.26.

Intermediate 99: (±)-benzyl (5-chloro-7-thien-3-yl-2,3-dihydro-l-benzofuran-2~ yl)methylcarbamate

Treatment of (±)-(5-chloro-7-thien-3-yl-2,3-dihydro- 1 -benzofuran-2- yl)methylamine (2.45 g, 8.11 mmol) with benzyl chloroformate (2.07 g, 12.15 mmol) and diisopropylethylamine (3.43 g, 24.32 mmol) generally according to the procedure described for Intermediate 12 provided 2.6 g (81 %) of (±)-benzyl (5-chloro-7-thien-3-yl- 2,3-dihydro-l-benzofuran-2-yl)methylcarbamate as a white solid, mp 90-92 ⁰ C; Anal, calcd. for C ₂ IH ₁₈ ClNO ₃ S: C, 63.07; H, 4.54; N, 3.50. Found: C, 63.44; H, 4.51; N, 3.43.

Chiral HPLC separation of (±)-benzyl (5-chloro-7-thien-3-yl-2,3-dihydro-l-benzofuran- 2-yl)methylcarbamate (Chiralpak AD, hexane:ethanol 1 :1) provided two fractions. Fraction 1 (Rf = 11.538 min, (Chiralpak AD, hexane:ethanol 1:1); Fraction 2 (R^ = 17.694 min, (Chiralpak AD, hexane:ethanol 1 :1).

Intermediate 100: 2-(allyloxy)-l-bromo~4-fluorobenzene

Treatment of 2-bromo-5-fluorophenol (10.00 g, 0.052 mol) with potassium carbonate (29.30 g, 0.209 mol) and allyl bromide (7.60 g, 0.063 mol) generally according to the reaction procedure described for Intermediate 8 provided 12.1 g (99%) of 2- (allyloxy)-l-bromo-4-fluorobenzene as a colorless oil. Ry= 0.37 (silica, ethyl acetate:hexanes 1 :9); ¹ H NMR (DMSO-rf*) δ _H 7.58 (dd, IH); 7.05 (dd, IH); 6.75 (dt, IH); 6.02 (m, IH); 5.43 (d, IH); 5.27 (d, IH); 4.65 (m, 2H).

Intermediate 101: 2-aHyl-6-bromo-3-fluorophenol Treatment of 2-(allyloxy)-l-bromo-4-fluorobenzene (12.00 g, 0.052 mol) in refluxing mesitylene generally according to the reaction procedure described for Intermediate 8 provided 11.5 g (95%) of 2-allyl-6-bromo-3-fluorophenol as a pale yellow oil. Ry= 0.48 (silica, ethyl acetate :hexanes 1 :4); Anal, calcd. for C ₉ HgBrFO: C, 46.78; H,

3.49. Found: C, 47.59; H, 3.47.

Intermediate 102: (±)-(7-bromo-4-fluoro-2,3-dihydro-l-benzofuran-2-yl)methano l

Treatment of 2-allyl-6-bromo-3-fluoroρhenol (9.01 g, 0.039 mol) with 3- chloroperoxybenzoic acid (77%, 13.46 g, 0.06 mol) followed by potassium carbonate (13.82 g, 0.10 mol) generally according to the reaction procedure described for Intermediate 9 gave 6.71 g (70%) of (±)-(7-bromo-4-fluoro-2,3-dihydro-l-benzofuran-2- yl)methanol as a white solid. Ry= 0.20 (silica, ethyl acetate :hexanes 1:4); mp 40-43 ⁰ C;

Anal, calcd. for C ₉ H ₈ BrFO ₂ -O^ H ₂ O: C, 43.13; H, 3.38. Found: C, 42.94; H, 3.15.

Intermediate 103: (±)-(7-bromo-4-fluoro-2,3-dihydro-l-benzofuran-2-yl)methyI 4- methylbenzenesulfonate

Treatment of (±)-(7-bromo-4-fluoro-2,3 -dihydro- 1 -benzofuran-2-yl)methanol

(6.21 g, 0.025 mol) with^-toluenesulfonyl chloride (5.26 g, 0.028 mol) in pyridine (120

mL) generally according to the procedure described for Intermediate 10 afforded 8.85 g (88%) of (±)-(7-bromo-4-fluoro-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate as a white solid. Ry= 0.60 (silica, ethyl acetate :hexanes 1:1); mp

100-103 °C; Anal, calcd. for Ci ₆ H ₁₄ BrFO ₄ S: C, 47.89; H, 3.52. Found: C, 47.89; H ₅ 3.68.

Intermediate 104: (±)-(4-fluoro-7-phenyl-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate

Treatment of (±)-(7-bromo-4-fluoro-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate (2.0 g, 4.98 mmol) with phenyl boronic acid (0.91 g, 7.22 mmol), dichlorobis(tri-o-tolylphosphine)-palladium(II) (0.392 g, 0.498 mmol), and potassium carbonate (1.72 g, 12.46 mmol) acording to the procedure described for Intermediate 37 gave 1.07 g (54%) of (±)-(4-fluoro-7-phenyl-2,3-dihydro-l-benzofuran- 2-yl)methyl 4-methylbenzenesulfonate as a white solid. Ry= 0.46 (silica, ethyl acetate:hexanes 1 :4); ¹ H NMR (DMSO-^) δ _H 7.70 (d, 2H); 7.53 (d, 2H); 7.40 (t, 2H); 7.32 (m, 4H); 6.77 (t, IH); 5.15 (m, IH); 4.31 (dd, IH); 4.22 (dd, IH); 3.30 (dd, IH, obscured by H2O peak); 3.01 (dd, IH).

Intermediate 105: (±)-[4-fluoro-7~(2-methylphenyl)-2,3-dihydro-l-benzofuran-2 - yl] methyl 4-methylbenzenesulfonate

Treatment of (±)-(7-bromo-4-fluoro-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate (2.05 g, 5.11 mmol) with 2-methylphenyl boronic acid (1.04 g, 7.66 mmol), dichlorobis(tri-o-tolylphosphine)-palladium(II) (0.201 g, 0.255 mmol), and potassium carbonate (1.77 g, 12.77 mmol) generally according to the procedure described for Intermediate 37 provided 1.38 g (65%) of (±)-[4-fluoro-7-(2-methylphenyl)-2,3- dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate as a white solid. Ry= 0.34

(silica, ethyl acetate :hexanes 1.5:8.5); Anal, calcd. for C23H21FO4S: C, 66.97; H, 5.13. Found: C, 66.95; H, 4.76.

Intermediate 106: 2-allyl-6-bromo-4-fhiorophenol

Treatment of l-(allyloxy)-2-bromo-4-fluorobenzene (23.90 g, 0.103 mol) in refluxing mesitylene (50 mL) generally according to the procedure described for Intermediate 8 provided 23.44 g (99%) 2-allyl-6-bromo-4-fluorophenol as a brown oil. Ry = 0.64 (silica, ethyl acetate ihexanes 1 : 19); Anal, calcd. for CpHgBrFO: C, 46.78; H, 3.49. Found: C, 49.19; H, 3.59.

Intermediate 107: (±)-(7-bromo-5-fluoro~2,3-dihydro-l-benzofuran-2-yl)methano l

Treatment of 2-allyl-6-bromo-4-fluorophenol (25.1 g, 0.109 mol) with 3- chloroperoxybenzoic acid (77%, 56.24 g, 0.326 mol) followed by potassium carbonate (62.19 g, 0.45 mol) generally according to the procedure described for Intermediate 9 provided 20.98 g (78%) of (±)-(7-bromo-5-fluoro-2,3-dihydro-l-benzofuran-2- yl)methanol as a white solid. Ry= 0.54 (silica, ethyl acetate:hexanes 1:1); mp 53-57 °C;

Anal, calcd. for C ₉ H ₈ BrFO ₂ -Cl C-^H ₈ O ₂ : C, 44.13; H, 3.47. Found: C, 44.17; H, 3.16.

Intermediate 108: (±)-(7~bromo-5-fluoro-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate

Treatment of (±)-(7-bromo-5-fluoro-2,3-dihydro- 1 -benzofuran-2-yl)methanol (11.5 g, 0.047 mol) with/?-toluenesulfonyl chloride (9.76 g, 0.051 mol) generally according to the procedure described for Intermediate 10 gave 12.5O g (66%) (±)-(7- bromo-5-fluoro-2,3-dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate as a white solid. Ry= 0.44 (silica, ethyl acetate :hexanes 1:4); mp 84-86 °C; Anal, calcd. for

Ci ₆ Hi4BrFθ4S: C, 47.89; H, 3.52. Found: C, 47.65; H, 3.63.

Intermediate 109: (±)-(5-fluoro-7-phenyl-2,3-dihydro-l-benzofuran-2-yl)methyI 4- methylbenzenesulfonate

Treatment of (±)-(7-bromo-5-fluoro-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate (2.00 g, 4.98 mmol) with phenyl boronic acid (0.912 g, 7.48 mmol), dichlorobis(tri-o-tolylphosphine)palladium(II) (0.196 g, 0.249 mmol), and potassium carbonate (1.72 g, 12.46 mmol) generally according to the procedure described for Intermediate 37 gave 1.62 g (82%) of (±)-(5-fluoro-7-phenyl-2,3-dihydro-l-

benzofuran-2-yl)methyl 4-methylbenzenesulfonate as a yellow oil. Rf= 0.54 (silica, ethyl acetate.-hexanes 1 :4); Anal, calcd. for C22Hi9FO4S-0.2 C-JHgC^: C, 65.82; H, 4.99. Found: C, 65.77; H, 4.99.

Intermediate 110: (±)-[5-fluoro-7-(2-methylphenyl)-2,3-dihydro-l-benzofuran-2 - yl]methyl 4-methylbenzenesulfonate

Treatment of (±)-(7-bromo-5-fluoro-2,3-dihydro- 1 -benzofuran-2-yl)methyl 4- methylbenzenesulfonate (2.00 g, 4.98 mmol) with 2-methylphenyl boronic acid (1.017 g, 7.48 mmol), dichlorobis(tri-o-tolylphosphine)palladium(II) (0.196 g, 0.249 mmol), and potassium carbonate (1.72 g, 12.46 mmol) generally according to the procedure described for Intermediate 37 provided 1.58 g (77%) of (±)-[5-fluoro-7-(2-methylphenyl)-2,3- dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate as a colorless oil. 0.47

(silica, ethyl acetate:hexanes 3:17); Anal, calcd. for C22H19FO4SO.2 C4H8O2: C,

66.46; H, 5.30. Found: C, 66.25; H ₅ 4.98.

Intermediate 111: (±)-[7-(2-chlorophenyl)-5-fluoro-2,3-dihydro-l-benzofuran-2 - yl] methyl 4-methylbenzenesulfonate

Treatment of (±)-(7-bromo-5-fluoro-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate (2.00 g, 4.98 mmol) with 2-chlorophenyl boronic acid (1.17 g, 7.48 mmol), dichlorobis(tri-o-tolylphosphine)palladium(II) (0.196 g, 0.249 mmol), and potassium carbonate (1.72 g, 12.46 mmol) generally according to the procedure described for Intermediate 37 afforded 1.44 g (67%) of (±)-[7-(2-chlorophenyl)-5-fluoro-2,3- dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate as a white solid. Rf= 0.26

(silica, ethyl acetate :hexanes 3:17); Anal, calcd. for C22H18CIFO4S: C, 61.04; H, 4.19. Found: C, 61.02; H, 3.95.

Intermediate 112: (±)-[5-fluoro-7-(2-fluorophenyl)-2,3-dihydro-l-benzofuran-2 - yl] methyl 4-methylbenzenesulfonate

Treatment of (±)-(7-bromo-5-fluoro-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate (2.00 g, 4,98 mmol) with 2-fluorophenyl boronic acid (1.05 g, 7.48 mmol), dichlorobis(tri-o-tolylphosphine)palladium(II) (0.196 g, 0.249 mmol), and potassium carbonate (1.72 g, 12.46 mmol) generally according to the procedure described

for Intermediate 37 gave 1.94 g (94%) of (±)-[5-fluoro-7-(2-fluorophenyl)-2,3-dihydro-l- benzofuran-2-yl] methyl 4-methylbenzenesulfonate as a yellow oil. Ry= 0.38 (silica, ethyl acetate:hexanes 3:17); Anal, calcd. for C22H18F2O4S: C ₃ 63.45; H ₅ 4.36. Found: C,

63.13; H ₃ 4.19.

Intermediate 113: (±)-{5-fluoro-7-[2-(trifluoromethyI)phenyl]-2,3-dihydro-l- benzofuran-2-yl}methyl 4-methyIbenzenesulfonate

Treatment of (±)-(7-bromo-5-fluoro-2 ₃ 3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate (4.01 g, 10.0 mmol) with 2-(trifluoromethyl)-phenyl boronic acid (2.85 g, 15.0 mmol), dichlorobis(tri-o-tolylphosρhine)ρalladium(II) (0.786 g, 1.00 mmol), and potassium carbonate (3.46 g, 25.00 mmol) generally according to the procedure described for Intermediate 37 provided 4.34 g (93%) of (±)-{5-fluoro-7-[2- (trifluoromethyl)phenyl]-2,3-dihydro-l-benzofuran-2-yl}methy l 4- methylbenzenesulfonate as a yellow oil. Kf- 0.54 (silica, ethyl acetate :hexanes 3:7); Anal, calcd. for C ₂₃ H ₁₈ F^S: C, 59.22; H, 3.89. Found: C, 60.19; H, 4.29.

Intermediate 114: (±)-benzyl [5-fluoro-7-(2-methylphenyl)-2,3-dihydro-l- b enzof ur an-2-y 1] methylcarb amate

Treatment of (±)-l-[5-fluoro-7-(2-methylphenyl)-2,3-dihydro-l-benzofuran -2- yl]methanamine (3.11 g, 12.1 mmol) with diisopropylethylamine (2.34 g, 18.1 mmol) and benzyl chloroformate (2.27 g, 13.3 mmol) generally according to the procedure described for Intermediate 12 gave 4.35 (92%) of (±)-benzyl [5-fluoro-7-(2-methylphenyl)-2,3- dihydro-l-benzofuran-2-yl]methylcarbamate as a colorless oil. Kf= 0.83 (silica, ethyl acetate:hexanes 1:9); Anal, calcd. for C ₂₄ H ₂₂ FO ₃ -O^ H ₂ O: C, 72.97; H, 5.72; N ₃ 3.55. Found: C ₃ 72.8; H, 5.72; N, 3.48. Chiral HPLC separation of (±)-benzyl [5-fluoro-7-(2- methylphenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methylcarbamate (Chiralcel OD ₃ hexanedsopropanol 8:2) provided two fractions. Fraction 1 (R^ = 7.269 min, Chiralcel

OD, hexane.-isopropanol 8:2); Fraction 2 (R^ = 8.449 min, Chiralcel OD, hexane:isopropanol 8:2).

Intermediate 115: (±)-benzyI [7-(2-chIorophenyl)-5-fluoro-2,3-dihydro-l- benzofuran-2-yl]methylcarbamate

Treatment of (±)-l-[7-(2-chlorophenyl)-5-fluoro-2,3-dihydro-l-benzofuran -2- yljmethanamine (2.92 g, 10.5 mmol) with diisopropylethylamine (1.70 g, 13.1 mmol) and benzyl chloroformate (1.97 g, 11.6 mmol) generally according to the procedure described for Intermediate 12 provided 3.02 (70%) of (±)-benzyl [7-(2-chlorophenyl)-5-fluoro-2,3- dihydro-l-benzofuran-2-yl]methylcarbamate as a colorless oil. Ry= 0.76 (silica, ethyl acetate:hexanes 1:9); Anal, calcd. for C ₂ 3Hi9ClFNC>3-0.5 H ₂ O: C, 65.64; H ₅ 4.79; N,

3.33. Found: C, 65.28; H, 4.73; N, 3.18. Chiral HPLC separation of (±)-benzyl [7-(2- chlorophenyl)-5-fluoro-2,3-dihydro-l-benzofuran-2-yl]methylc arbamate (Chiralcel OJ, hexane:ethanol 1 :1) provided two fractions. Fraction 1 (R^ = 9.322 min, Chiralcel OJ, hexane:ethanol 1 :1); Fraction 2 (R^ = 13.646 min, Chiralcel OJ, hexane:ethanol 1:1).

Intermediate 116: (±)-benzyl {5-fluoro-7-[2-(trifluoromethyl)phenyl]-2,3-dihydro-l- benzofuran-2-yl}methykarbamate

Treatment of (±)- 1 - { 5-fluoro-7- [2-(trifluoromethyl)phenyl] -2,3 -dihydro- 1 - benzofuran-2-yl}methanamine (1.87 g, 5.38 mmol) with diisopropylethylamine (1.74 g, 13.4 mmol) and benzyl chloroformate (1.01 g, 5.92 mmol) following the procedure described for Intermediate 12 provided 2.03 (85%) of (±)-benzyl {5-fluoro-7-[2- (trifluoromethyl)phenyl]-2,3-dihydro-l-benzofuran-2-yl}methy lcarbamate as a white solid. Ry= 0.69 (silica, ethyl acetate :hexanes 1:9); mp 76-80 °C; Anal, calcd. for

C24H19F4NO3: C, 64.72; H, 4.3; N, 3.14. Found: C, 65.01; H, 4.3; N, 2.99.

Intermediate 117: (±)-(7~bromo-4,5-difluoro-2,3-dihydro-l-benzofuran-2-yl)met hyl 4-methylbenzenesulfonate

Treatment of 2-allyl-6-bromo-3,4-difluorophenol (5.0 g, 0.020 mol) with 3- chloroperoxybenzoic acid (77%, 8.1 g, 0.036 mol) followed by potassium carbonate (6.94 g, 0.050 mol) generally according to the procedure described for Intermediate 9 afforded (±)-(7-bromo-4,5-difluoro-2,3-dihydro-l-benzofuran-2-yl)met hanol a brown oil. Treatment of the alcohol with diisopropylethylamine (2.57 g, 0.020 mol), p- toluenesulfonyl chloride (2.28 g, 0.012 mol), and 4-(dimethylamino)pyridine (0.29 g,

2.375 mmol) generally according to the procedure described for Intermediate 45 gave 2.9

g (3.5%) ot (±)-(7-bromo-4,5-difluoro-2,3-dihydro-l-benzofuran-2-yl)met hyl 4- methylbenzenesulfonate as a white solid. Ry= 0.46 (silica, ethyl acetate:hexanes 1 :3); ¹ H

NMR (DMSO-40 δ _H 7.73 (d, 2H); 7.50 (dd, IH); 7.43 (d, 2H); 5.15 (m, IH); 4.3 (dd, IH); 4.22 (dd, IH); 3.45 (dd, IH); 3.08 (dd, IH).

Intermediate 118: (±)-(4,5-difluoro-7-phenyl-2,3-dihydro-l-benzofuran-2-yl)me thyl 4-methylbenzenesulfonate

To a solution of (±)-(7-bromo-4,5-difluoro-2,3-dihydro-l-benzofuran-2- yl)methyl 4-methylbenzenesulfonate (1.5 g, 3.59 mmol) in dioxane (30 niL) was added phenylboronic acid (0.656 g, 5.38 mmol), dichloro[l,l'- bis(diphenylphosphino)ferrocene]palladium(II)dichloromethane adduct (0.293 g, 0.359 mmol), and potassium carbonate (0.993 g, 7.18 mmol) and the reaction mixture was heated at reflux for 48 h. The reaction mixture was filtered (celite), rinsed (ethyl acetate), and the combined organic layers were washed with water (100 mL), aqueous sodium chloride (75 mL), dried (sodium sulfate) and the solvent was removed in vacuo to provide a crude solid. Purification by column chromatography (silica, ethyl acetate :hexane 1:9) afforded 1.19 g (80%) of (±)-(4,5-difluoro-7-phenyl-2,3-dihydro-l-benzofuran-2- yl)methyl 4-methylbenzenesulfonate as a white solid. Ry= 0.76 (silica, ethyl acetate:hexanes 1 :9); ¹ H NMR (DMSO-^) δ _H 7.69 (d, 2H); 7.50 (dd, IH); 7.56 (d, 2H); 7.35 (m, 6H); 5.14 (m, IH); 4.30 (dd, IH); 4.20 (dd, IH); 3.39 (dd, IH); 3.05 (dd, IH).

Intermediate 119: (±)-(4,5-difluoro-7-phenyl-2,3-dihydro-l-benzofuran-2-yI)me thyl azide

To a solution of (±)-(4,5-difmoro-7-phenyl-2,3-dihydro-l-benzofuran-2- yl)methyl 4-methylbenzenesulfonate (1.0 g, 2.40 mmol) in λζN-dimethylformamide (25 mL) was added sodium azide (0.781 g, 12.02 mmol) and the reaction mixture was heated to 70 ⁰ C and allowed to stir for 3 h. The reaction mixture was allowed to cool and the solvent was removed in vacuo to provide a crude solid. The residue was suspended in ethyl acetate (100 mL) and washed with water (50 mL) and aqueous sodium chloride (50 mL), was dried (sodium sulfate) and the solvent was removed in vacuo to give a crude solid. Purification by flash column chromatography (silica, ethyl acetate :hexanes 1:9) provided 0.68 g (99%) of (±)-(4,5-difluoro-7-phenyl-2,3-dihydro-l-benzofuran-2-

yljmethyl azide as a white solid. Ry= 0.93 (silica, ethyl acetate :hexanes 1:9); ¹ H NMR

(DMSO-^) δ _H 7.65 (d, 2H); 7.41 (m, 3H); 7.31 (t, IH); 5.15 (m, IH); 3.64 (m, 2H); 3.46 (dd, IH); 3.10 (dd, IH).

Intermediate 120: (±)-[4,5-difluoro-7-(2-methyIphenyI)-2,3-dihydro-l-benzofur an-2- yl]methyl 4-methylbenzenesulfonate

Treatment of (±)-(7-bromo-4,5-difluoro-2,3-dihydro-l-benzofuran-2-yl)met hyl 4-methylbenzenesulfonate (1.5 g, 3.59 mmol) with 2-methylphenyl boronic acid (0.732 g, 5.38 mmol), dichloro[l,l'~ bis(diphenylphosphino)ferrocene]palladium(II)dichloromethane adduct (0.293 g, 0.359 mmol), and potassium carbonate (0.993 g, 7.18 mmol) generally according to the procedure described for Intermediate 118 afforded 1.3 g (84%) of (±)-[4,5-difluoro-7-(2- methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate as a white solid. Ry= 0.72 (silica, ethyl acetate:hexanes 1 :4); ¹ H NMR (OMSO-d ₆ ) δ _H 7.67 (d, 2H); 7.38 (d, 2H); 7.20 (m, 3H); 7.05 (m, 2H); 5.05 (m, IH); 4.22 (dd, 2H); 4.13 (dd, IH); 3.40 (dd, IH); 3.02 (dd, IH); 2.05 (s, 3H).

Intermediate 121: (±)-[4,5-difluoro-7-(2-methyIphenyI)-2,3-dihydro-l-benzofur an-2- yl] methyl azide Treatment of (±)-[4,5-difluoro-7-(2-methylphenyl)-2,3-dihydro- 1 -benzofuran-2- yl]methyl 4-methylbenzenesulfonate (1.3 g, 3.02 mmol) with sodium azide (0.983 g, 15.11 mmol) generally according to the procedure described for intermediate 98 gave 0.82 g (90%) of (±)-[4,5-difluoro-7-(2-methylρhenyl)-2,3-dihydro-l-benzofu ran-2- yljmethyl azide as a colorless oil. Ry= 0.69 (silica, ethyl acetate :hexanes 1:4); ¹ H NMR (DMSO-^) δ _H 7.25 (d, 2H); 7.14 (m, 3H); 5.06 (m, IH); 3.67 (dd, IH); 3.55 (dd, IH); 3.46 (dd, IH); 3.11 (dd, IH); 2.15 (s, 3H).

Intermediate 122: (±)-(5-chIoro-7-methoxy-2-methyI-2,3-dihydro-l-benzofuran-2 - yl)methyl 4-methylbenzenesulfonate Treatment of 4-chloro-2-methoxyphenol (15.00 g, 0.10 mol) with sodium hydride

(4.4 g, 0.11 mol, 60 wt.%) and 3-chloro-2-methylpropene (12.00 g, 0.12 mol) generally according to the procedure described for Intermediate 13 provided 19.3 g (91%) of 4-

chloro-2-methoxy-l-[(2-methylprop-2-enyl)oxy]benzene as a colorless oil. Treatment of the allyl ether in refluxing mesitylene generally according to the procedure described for Intermediate 8 afforded 15.5 g (78%) of 4-chloro-2-methoxy-6-(2-methylprop-2- enyl)phenol as a pale yellow oil. Treatment of 4-chloro-2-methoxy-6-(2-methylprop-2- enyl)phenol (10.00 g, 0.047 mol) with 3-chloroρeroxybenzoic acid (20.00 g, 0.089 mol, 77%) followed by potassium carbonate (20.00 g, 0.145 mol) generally according to the Procedure described for Intermediate 9 provided 8.00 g (74%) of (±)-(5-chloro-7- methoxy-2-methyl-2,3-dihydro-l-benzofuran-2-yl)methanol as a light yellow oil. Treatment of (±)-(5-chloro-7-methoxy-2-methyl-2,3-dihydro-l-benzofuran-2 -yl)methanol (10.8 g, 0.047 mol) withjσ-toluenesulfonyl chloride (13.5 g, 0.071 mol), diisopropylethylamine (12.15 g, 0.094 mol), and 4-(dimethylamino)pyridine (0.35 g, 2.83 mmol) generally according to the procedure described for Intermediate 45 gave 13.8 g (76%) of (±)-(5-chloro-7-methoxy-2-methyl-2,3-dihydro-l-benzofuran-2 -yl)methyl 4- methylbenzenesulfonate as a white solid, mp 113-115 ⁰ C; Anal, calcd. for C ₁₈ H ₁₉ ClO ₅ S: C, 56.47; H, 5.00. Found: C,55.82; H, 4.94.

Intermediate 123: (±)-(5-chloro-7-hydroxy-2-methyl-2,3-dihydro-l-benzofuran-2 - yl)methyl 4-methylbenzenesulfonate

Treatment of (±)-(5-chloro-7-methoxy-2-methyl-2,3-dihydro-l-benzofuran-2 - yl)methyl 4-methylbenzenesulfonate (13.80 g, 0.036 mol ) with hydrogen bromide (200 mL, 30 wt. % in acetic acid) generally according to the procedure described for Intermediate 46 afforded 11.7 g (80%) of (±)-(5-chloro-7-hydroxy-2-methyl-2,3-dihydro- l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate as a white solid, mp 135-137 °C; Anal, calcd. for C ₁₇ H ₁₇ ClOsS: C, 55.36; H, 4.65. Found: C, 54.35; H, 4.52.

Intermediate 124: (±)-(5-chloro~2-methyl-7-{[(trifluoromethyl)sulfonyl]oxy}-2 ,3- dihydro-l~benzofuran-2-yl)methyI 4-methylbenzenesulfonate

Treatment of (±)-(5-chloro-7-hydroxy-2-methyl-2,3-dihydro- 1 -benzofuran-2- yl)methyl 4-methylbenzenesulfonate (11.7g, 0.032 mol) with trifluoromethanesulfonic anhydride (10.34 g, 0.037 mol) and diisopropylethylamine (4.74 g, 0.037 mol) generally according to the procedure described for Intermediate 7 provided 13.0 g (82%) of (±)-(5- chloro-2-methyl-7- { [(trifluoromethyl)sulfonyl]oxy } -2,3 -dihydro- 1 -benzofuran-2-

yljmethyl 4-methylbenzenesulfonate as a white solid, mp 100-102 ⁰ C; Anal, calcd. for C ₁₈ H ₁ ^ClF ₃ O ₇ S ₂ : C ₅ 43.16; H, 3.22. Found: C, 43.07; H, 3.04.

Intermediate 125: (-)-benzyl [(7-fer^butyl-5-methoxy-2,3-dihydro-l-benzofuran-2- yl)methyl] carbamate

Fraction 1 obtained as a colorless oil from the chiral HPLC separation of (±)- benzyl (7-tert-butyl-5-methoxy-2,3-dihydro-l-benzofuran-2-yl)methyl carbamate (R/ =

4.39 min, Chiralpak OD, 2-butanol: carbon dioxide 2:8). [α]" = -17.46 (c 10.0 in methanol); Anal, calcd. for C22H27NO4 C, 71.52; H, 7.37; N, 3.79. Found C, 71.2; H, 7.61; N, 3.62.

Intermediate 126: (+)-benzyl [(7-fert-butyl-5-methoxy-2,3-dihydro-l-benzofuran-2- yl)methyl] carbamate i

Fraction 2 obtained as a colorless oil from the chiral HPLC separation of (±)- benzyl [(7-tert-butyl-5-methoxy-2,3-dihydro-l-benzofuran-2-yl)methy l]carbamate (R^ -

5.07 min, Chiralpak OD, 2-butanol:carbon dioxide 2:8). [α]^ ⁵ = +22.18 (c 10.0 in methanol); Anal, calcd. for C22H27NO4 C, 71.52; H, 7.37; N, 3.79. Found C, 70.33; H, 7.49; N, 3.5.

Intermediate 127: (±)-{7-[(l£)-3,3-dimetliylbut-l-enyI]-2,3-dihydro-l-benzof uran-2- yl}methyl 4-methylbenzenesulfonate

Treatment of (±)-(7-bromo-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate (8.0 g, 20.87 mmol) with [E]-2-fert-butylvinylboronic acid (4.01 g, 31.31 mmol), dichlorobis(tri-o-tolylphosphine)-palladium(II) (0.82 g, 1.04 mmol), and potassium carbonate (7.21 g, 52.19 mmol) generally according to the procedure described for Intermediate 37 provided 6.54 g (81%) of (±)-{7-[(l£)-3,3-dimethylbut-l-enyl]-2,3- dihydro-l-benzofuran-2-yl}methyl 4-methylbenzenesulfonate as a white solid, mp 85-88 ⁰ C; Anal, calcd. for C22H26O4S: C, 68.37; H, 6.78. Found: C, 68.27; H, 6.86.

Intermediate 128: (±)-{7-[(£)-2-phenylvinyl]-2,3-dihydro-l-benzofuran-2-yI}m ethyl 4-methylbenzenesulfonate

Treatment of (±)-(7-bromo-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate (8.0 g, 20.9 mmol) with trørø-2-phenylvinylboronic acid (4.63 g, 31.3 mmol), dichlorobis(tri-o-tolylphosphine)-palladium(II) (0.82 g, 1.04 mmol), and potassium carbonate (7.21 g, 52.2 mmol) generally according to the procedure described for Intermediate 37 provided 6.59 g (78%) of (±)-{7-[(£)-2-phenylvinyl]-2,3-dihydro-l~ benzofuran-2-yl} methyl 4-methylbenzenesulfonate as a light yellow solid, mp 120-122 ⁰ C; Anal, calcd. for C24H22O4S: C, 70.91; H, 5.45. Found: C, 70.78; H, 5.56.

Intermediate 129: (±)-benzyl {[4-(4-methylphenyl)-2,3-dihydro-l-benzofuran-2- yl]methyl}carbamate

Treatment of (±)- 1 - [4-(4-methylphenyl)-2,3-dihydro- 1 -benzofuran-2- yl]methanamine (1.94 g, 7.03 mmol) with diisopropylethylamine (1.36 g, 10.55 mmol) followed by benzyl chloroformate (1.32 g, 7.74 mmol) generally according to the procedure described for Intermediate 12 provided 2.36 g (90%) of (±)-benzyl {[4-(4- methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}carbamate as a white solid, mp 134-136 °C; Anal, calcd. for C24H23NO3: C, 77.19; H, 6.21; N, 3.75. Found: C, 77.08;

H, 6.3; N, 3.69.

Intermediate 130: (±)-benzyl ({4-[2-(trifluoromethyl)phenyl]-2,3-dihydro-l- benzofuran~2-yl}methyl)carbamate

Treatment of (±)-l-{4-[2-(trifluoromethyl)phenyl]-2,3-dihydro-l-benzofur an-2- yljmethanamine (2.21 g, 6.7 mmol) with diisopropylethylamine (1.3 g, 10.05 mmol) followed by benzyl chloroformate (1.25 g, 7.37 mmol) generally according to the procedure described for Intermediate 12 provided 2.6 g (91%) of (±)-benzyl ({4-[2- (trifluoromethyl)phenyl]-2,3-dihydro-l-benzofuran-2-yl}methy l)carbamate as a colorless oil. Anal, calcd. for C24H20F3NO3: C, 67.44; H, 4.72; N, 3.28. Found: C, 67.5; H, 4.7;

N, 3.13. Chiral HPLC separation of (±)-benzyl ({4-[2-(trifluoromethyl)phenyl]-2,3- dihydro- 1 -benzofuran-2-yl } methyl)carbamate (Chiralcel OJ, ethanol :hexane 1 :1) provided two fractions. Fraction 1 (R^ = 5.701 min, Chiralcel OJ, ethanol :hexane 1 :1);

Fraction 2 (R^ = 7.122 min, Chiralcel OJ, ethanol :hexane 1:1).

Intermediate 131: (-)-benzyl ({4-[2-(trifluoromethyl)phenyl]-2,3-dihydro-l- benzofuran-2-yl}methyl)carbamate

Fraction 1 obtained as a colorless oil from the chiral HPLC separation of (±)- benzyl ({4-[2-(trifluoromethyl)phenyl]-2,3-dihydro-l-benzofυran-2- yl}methyl)carbamate (R, = 5.701 min, Chiralcel OJ, ethanol:hexane 1 :1). [α]o = -61.46 (c 10.0 in methanol); Anal, calcd. for C24H20F3NO3: C, 67.44; H, 4.72; N, 3.28. Found C, 67.52; H, 4.67; N ₅ 3.11.

Intermediate 132: (+)-benzyl ({4-[2-(trifluoromethyl)phenyl]-2,3-dihydro-l- benzofuran-2-yl}methyI)carbamate

Fraction 2 obtained as a colorless oil from the chiral HPLC separation of (±)- benzyl ({4-[2-(trifluoromethyl)phenyl]-2,3-dihydro-l-benzofuran-2-y l}methyl)carbamate (R, = 7.122 min, Chiralcel OJ, ethanol:hexane 1 :1). [<X] _D = +60.44 (c 10.0 in methanol); Anal, calcd. for C24H20F3NO3: C, 67.44; H ₅ 4.72; N ₅ 3.28. Found C, 67.03; H ₅ 4.62; N ₅ 3.2.

Intermediate 133: (±)-[4-(2,6-dimethylphenyl)-2,3-dihydro-l-benzofuran-2- yl]methyl 4-methyIbenzenesulfonate Treatment of (±)-(4-bromo-2 ₅ 3-dihydro- 1 -benzofuran-2-yl)methyl 4- methylbenzenesulfonate (1.5 g, 3.32 mmol) with 2,6-dimethylphenylboronic acid (2.35 g, 15.66 mmol), tetrakis(triphenylphosphine)palladium(0) (0.452 g, 0.394 mmol), and barium hydroxide octahydrate (6.17 g, 19.57 mmol) generally according to the procedure described for Intermediate 50 provided 2.27 g (71%) of (±)-[4-(2,6-dimethylphenyl)-2,3- dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate as a colorless oil. Anal, calcd. for C24H24O4S: C, 70.56; H ₅ 5.92. Found: C ₅ 69.72; H ₅ 5.87.

Intermediate 134: (±)-benzyl {[4-(2,6-dimethylphenyl)-2,3-dihydro-l-benzofuran-2~ y I] methyl} carb amate Treatment of (±)-l-[4-(2,6-dimethylphenyl)-2,3-dihydro-l-benzofuran-2- yl]methanamine (1.2 g, 4.14 mmol) with diisopropylethylamine (0.803 g ₅ 6.21 mmol) followed by benzyl chloroformate (0.848 g, 4.97 mmol) generally according to the

procedure described for Intermediate 12 provided 1.52 g (95%) of (±)-benzyl {[4-(2,6- dimethylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}carbama te as a colorless oil. Anal, calcd. for C25H25NO3: C, 77.49; H, 6.5; N, 3.61. Found: C, 76.66; H, 6.31; N,

3.44. Chiral HPLC separation of (±)-benzyl {[4-(2,6-dimethylphenyl)-2,3-dihydro-l- benzofuran-2-yl]methyl} carbamate (Chiralcel OD, ethanol) provided two fractions.

Fraction 1 (R _t = 4.818 min, Chiralcel OD, ethanol); Fraction 2 (Rf = 6.985 min, Chiralcel

OD, ethanol).

Intermediate 135: (+)-benzyl {[4-(2,6-dimethylphenyl)-2,3-dihydro-l-benzofuran-2- yl]methyl}carbamate

Fraction 1 obtained as a colorless oil from the chiral HPLC separation of (±)- benzyl {[4-(2,6-dimethylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methy l}carbamate (R^ =

4.818 min, Chiralcel OD, ethanol). [a]^ ⁵ = +60.96 (c 10.0 in methanol); Anal, calcd. for C25H25NO3: C, 77.49; H, 6.5; N, 3.61. Found: C, 77.11; H, 6.26; N, 3.38.

Intermediate 136: (-)-benzyl {[4-(2,6-dimethylphenyl)-2,3-dihydro-l-benzofuran-2- y 1] methyl} carb amate

Fraction 2 obtained as a colorless oil from the chiral HPLC separation of (±)- benzyl {[4-(2,6-dimethylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methy l}carbamate (R^ = 6.985 min, Chiralcel OD, ethanol). [αβ ⁵ = -59.24 (c 10.0 in methanol); Anal, calcd. for C25H25NO3: C, 77.49; H, 6.5; N, 3.61. Found: C, 76.91; H, 6.37; N, 3.46.

Intermediate 137: (±)-(7-thien-3-yl-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate Treatment of (±)-(7-bromo-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate (0.50 g, 1.305 mmol) with 3-thiopheneboronic acid (0.334 g, 2.61 mmol), dichlorobis(tri-o-tolylphosphine)-palladium(II) (0.051 g, 0.065 mmol), and potassium carbonate (0.45 g, 3.26 mmol) generally according to the procedure described for Intermediate 37 provided 0.389 g (77%) of (±)-(7-thien-3-yl-2,3-dihydro-l- benzofuran-2-yl)methyl 4-methylbenzenesulfonate as a light yellow solid, mp 90-92 ⁰ C; Anal, calcd. for C20H18O4S2: C, 62.15; H, 4.69. Found: C, 62.2; H ₅ 4.72.

Intermediate 138: (±)-{7-[2-(trifluoromethyl)phenyl]-2,3-dihydro-l-benzofuran -2- yl}methyl 4-methylbenzenesulfonate

Treatment of (±)-(7-bromo-2,3-dihydro-l-benzofuran-2-yl)methyl A- methylbenzenesulfonate (10.0 g, 26.10 mmol) with 2-(trifluoromethyl)phenylboronic acid (7.43 g, 39.12 mmol), dichlorobis(tri-o-tolylphosphine)-palladium(II) (1.02 g, 1.30 mmol), and potassium carbonate (9.01 g, 65.19 mmol) generally according to the procedure described for Intermediate 37 provided 8.46 g (75%) of (±)-{7-[2- (trifluoromethyl)phenyl]-2,3-dihydro-l-benzofuran-2-yl}methy l 4- methylbenzenesulfonate as a tan solid, mp 116-118 ⁰ C; Anal, calcd. for C23H19F3O4S:

C, 61.60; H, 4.27. Found: C, 61.91; H, 4.23.

Intermediate 139: (±)-[7-(2-chlorophenyI)-2,3-dihydro-l-benzofuran-2-yI]methy I 4- methylbenzenesulfonate Treatment of (±)-(7-bromo-2,3-dihydro- 1 -benzofuran-2-yl)methyl 4- methylbenzenesulfonate (3.00 g, 7.83 mmol) with 3-chlorophenylboronic acid (1.84 g, 11.74 mmol), dichlorobis(tri-o-tolylphosphine)-palladium(II) (0.308 g, 0.391 mmol), and potassium carbonate (2.70 g, 19.57 mmol) generally according to the procedure described for Intermediate 37 provided 2.35 g (72%) of (±)-[7-(2-chlorophenyl)-2,3-dihydro-l- benzofuran-2-yl]methyl 4-methylbenzenesulfonate as a tan solid, mp 100-103 °C; Anal, calcd. for C22H19CIO4S: C, 63.69; H, 4.62. Found: C, 63.43; H, 4.69.

Intermediate 140: (+)-benzyl {[7-(2-chlorophenyI)-2,3-dihydro-l~benzofuran-2- y 1] m ethyl} carbamate Fraction 1 obtained as a colorless oil from the chiral HPLC separation of (±)- benzyl {[7-(2-chlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}ca rbamate (R^ =

9.655 min, Chiralcel OJ, hexane:ethanol 1 :1). [α]^ ⁵ = +10.48 (c 10.0 in methanol); Anal, calcd. for C23H20CINO3: C, 70.14; H, 5.12; N, 3.56. Found C, 69.45; H, 4.92; N, 2.94.

Intermediate 141: (-)-benzyl {[7-(2-chIorophenyl)-2,3-dihydro-l-benzofuran-2- yl] methyl} carbamate

Fraction 2 obtained as a colorless oil from the chiral HPLC separation of (±)- benzyl {[7-(2-chlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}ca rbamate (R/ = 16.300 min, Chiralcel OJ, hexane:ethanol 1 :1). [α]^ ⁵ = -9.64 (c 10.0 in methanol); Anal, calcd. for C23H20CINO3: C, 70.14; H, 5.12; N ₃ 3.56. Found C ₃ 69.43; H, 5.06; N ₃ 3.19.

Intermediate 142: (±)-[7-(2-methylphenyl)-2,3-dihydro-l-benzofuran-2-yI]methy I 4- methylbenzenesulfonate Treatment of (±)-(7-bromo-2,3-dihydro- 1 -benzofuran-2-yl)methyl A- methylbenzenesulfonate (0.50 g, 1.305 mmol) with 3-methylphenylboronic acid (0.266 g, 1.96 mmol), dichlorobis(tri-o-tolylphosphine)-palladium(II) (0.051 g, 0.065 mmol), and potassium tert-butoxide (0.366 g, 3.26 mmol) generally according to the procedure described for Intermediate 37 provided 0.358 g (70%) of (±)-[7-(2-methylphenyl)-2,3- dihydro- 1 -benzofuran-2-yl]methyl 4-methylbenzenesulfonate as a white solid, mp 98-100 °C; Anal, calcd. for C23H22O4S: C, 70.03; H, 5.62. Found: C, 69.83; H ₃ 5.61.

Intermediate 143: (±)-[7-(2-fluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methy l 4- methylbenzenesulfonate Treatment of (±)-(7-bromo-2,3 -dihydro- 1 -benzofuran-2-yl)methyl A- methylbenzenesulfonate (0.500 g, 1.305 mmol) with 2-fluorophenylboronic acid (0.274 g, 1.96 mmol), dichlorobis(tri-o-tolylphosphine)-palladium(II) (0.051 g, 0.065 mmol), and potassium carbonate (0.45 g, 3.26 mmol) generally according to the procedure described for Intermediate 37 provided 0.422 g (81%) of (±)-[7-(2-fluorophenyl)-2,3-dihydro-l- benzofuran-2-yl]methyl 4-methylbenzenesulfonate as a yellow solid, mp 99-101 °C; Anal, calcd. for C22H19FO4S: C ₃ 66.32; H ₃ 4.81. Found: C, 65.16; H, 4.86.

Intermediate 144: (±)-[7-(2-methoxyphenyI)-2,3-dihydro-l-benzofuran-2-yl]meth yl 4-methylbenzenesulfonate Treatment of (±)-(7-bromo-2,3-dihydro- 1 -benzofuran-2-yl)methyl A- methylbenzenesulfonate (5.00 g, 13.04 mmol) with 2-methoxyphenylboronic acid (3.96 g,

26.09 mmol), dichlorobis(tri-o-tolylphosphine)-palladium(II) (0.532 g, 0.652 mmol), and

potassium carbonate (4.5 g, 32.62 mmol) generally according to the procedure described for Intermediate 37 provided 3.63 g (68%) of (±)-[7-(2-methoxyρhenyl)-2 ₃ 3-dihydro-l- benzofuran-2-yl]methyl 4-methylbenzenesulfonate as a yellow solid, mp 151-153 °C; Anal, calcd. for C23H22O5S: C, 67.3; H, 5.4. Found: C, 66.95; H, 5.43.

Intermediate 145: (±)-[7-(3-fluorophenyI)-2,3-dihydro-l-benzofuran-2-yl]methy l 4- methylbenzenesulfonate

Treatment of (±)-(7-bromo-2,3-dihydro-l-benzofuran-2-yl)m ethyl A- methylbenzenesulfonate (0.50 g, 1.305 mmol) with 3-fiuorophenylboronic acid (0.274 g, 1.96 mmol), dichlorobis(tri-o-tolylphosphine)-palladium(II) (0.051 g, 0.065 mmol), and potassium carbonate (0.45 g, 3.26 mmol) generally according to the procedure described for Intermediate 37 provided 0.392 g (75%) of (±)-[7-(3-fluorophenyl)-2,3-dihydro-l- benzofuran-2-yl]methyl 4-methylbenzenesulfonate as a light yellow solid, mp 88-90 ⁰ C; Anal, calcd. for C22H19FO4S: C, 66.32; H, 4.81. Found: C, 65.63; H ₃ 4.84.

Intermediate 146: (±)-benzyl {[7-(3-fluorophenyl)-2,3-dihydro-l-benzofuran-2- yl]methyl}carbamate

Treatment of (±)- 1 - [7-(3 -fluorophenyl)-2,3 -dihydro- 1 -benzofuran-2- yl]methanamine (798 g, 6.382.86 mmol) with diisopropylethylamine (0.554 g, 4.29 mmol) followed by benzyl chloroformate (0.536 g, 3.14 mmol) generally according to the procedure described for Intermediate 12 provided 1.01 g (94%) of (±)-benzyl {[7-(3- fluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}carbamate as a white solid. Rf-

0.41 (silica, ethyl acetate :hexanes 2:8); Anal, calcd. for C23H20FNO3: C ₃ 73.2; H, 5.34;

N, 3.71. Found: C, 72.96 H, 5.38; N, 3.59. Chiral HPLC separation of (±)-benzyl {[7-(3- fluorophenyl)-2 ₃ 3 -dihydro- 1 -benzofuran-2-yl]methyl } carbamate (Chiralpak OD, isopropanol:hexane 2:8) provided two fractions. Fraction 1 (R/ = 7.675 min, Chiralpak

OD, isopropanol:hexane 2:8); Fraction 2 (R^ = 9.182 min, Chiralpak OD ₃ isopropanol:hexane 2:8).

Intermediate 147: (+)-benzyl {[7-(3-fluorophenyl)-2,3-dihydro-l-benzofuran-2- yl]methyl}carbamate

.Fraction 1 obtained as a colorless oil from the chiral HPLC separation of (±)- benzyl {[7-(3-fluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}ca rbamate (R^ =

7.675 min, Chiralpak OD, isopropanol:hexane 2:8). [α]^ ⁵ = +41.76 (c 10.0 in methanol); Anal, calcd. for C23H20FNO3: C, 73.2; H ₅ 5.34; N, 3.71. Found C ₃ 73.01; H, 5.28; N ₅ 3.75.

Intermediate 148: (-)-benzyl {[7-(3-fluorophenyl)~2,3-dihydro-l-benzofuran-2- yl]methyl}carbamate

Fraction 2 obtained as a colorless oil from the chiral HPLC separation of (±)- benzyl {[7-(3-fluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}ca rbamate (Rf =

9.182 min, Chiralpak OD ₅ isopropanokhexane 2:8). [α]β = -34.44 (c 10.0 in methanol); Anal, calcd. for C23H20FNO3: C, 73.2; H ₅ 5.34; N ₅ 3.71. Found C ₅ 73.2; H, 5.39; N, 3.62.

Intermediate 149: (±)-[7-(3-methoxyphenyϊ)-2,3-dihydro-l-benzofuran-2-yI]met hyl 4-methylbenzenesulfonate

Treatment of (±)-(7-bromo-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate (5.00 g, 13.05 mmol) with 3-methoxyphenylboronic acid (2.97 g, 19.57 mmol), dichlorobis(tri-o-tolylphosphine)-palladium(II) (0.512 g, 0.652 mmol), and potassium carbonate (4.51 g, 32.62 mmol) generally generally according to the procedure described for Intermediate 37 provided 4.48 g (84%) of (±)-[7-(3-methoxyphenyl)-2,3- dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate as a white solid, mp 141- 142 ⁰ C; Anal, calcd. for C23H22O5S: C, 67.3; H ₅ 5.4. Found: C ₅ 66.51; H ₅ 5.41.

Intermediate 150: (±)-benzyI {[7-(3-methoxyphenyl)-2,3-dihydro-l-benzofuran-2- yl]methyl}carbamate

Treatment of (±)-l -[7-(3-methoxyphenyl)-2 ₅ 3-dihydro-l -benzofuran-2- yljmethanamine (2.4 g, 9.4 mmol) with diisopropylethylamine (1.82 g ₅ 14.10 mmol) followed by benzyl chloroformate (1.92 g ₅ 11.28 mmol) generally according to the procedure described for Intermediate 12 provided 3.28 g (90%) of (±)-benzyl {[7-(3- methoxyphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}carbamat e as a colorless oil. Ry=

0.51 (silica, ethyl acetate :hexanes 2:8); Anal, calcd. for C24H23NO4: C, 74.02; H, 5.95; N, 3.6. Found: C, 73.52; H, 6.06; N, 3.28. Chiral HPLC separation of (±)-benzyl {[7-(3- methoxyphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}carbamat e (Chiralpak OD, ethanol) provided two fractions. Fraction 1 (R^ = 6.220 min, Chiralpak OD, ethanol); Fraction 2 (R^ = 8.373 min, Chiralpak OD ethanol).

Intermediate 151: (+)-benzyl {[7-(3-methoxyphenyl)-2,3-dihydro-l-benzofuran-2- yl] methyl} carbamate

Fraction 1 obtained as a colorless oil from the chiral HPLC separation of (±)- benzyl { [7-(3-methoxyphenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methyl} carbamate (R^ =

6.220 min, Chiralpak OD, ethanol). [α]" = +26.94 (c 10.0 in methanol); Anal, calcd. for C24H23NO4: C, 74.02; H, 5.95; N, 3.6. Found: C, 73.48; H, 5.98; N, 3.46.

Intermediate 152: (-)-benzyl {[7-(3-methoxyphenyl)-2,3-dihydro-l-benzofuran-2- yl] methyl} carbamate

Fraction 2 obtained as a colorless oil from the chiral HPLC separation of (±)- benzyl {[7-(3-methoxyphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}c arbamate (R^ =

8.373 min, Chiralpak OD ethanol). [α]^ ⁵ = -26.96 (c 10.0 in methanol); Anal, calcd. for C24H23NO4: C, 74.02; H, 5.95; N, 3.6. Found: C, 73.52; H, 6.01; N, 3.45.

Intermediate 153: (±)-[7-(3-chlorophenyl)~2,3-dihydro-l-benzofuran-2-yl]methy l 4- methylbenzenesulfonate

Treatment of (±)-(7-bromo-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate (0.50 g, 1.305 mmol) with 3-chlorophenylboronic acid (0.306 g, 1.96 mmol), dichlorobis(tri-o-tolylphosphine)-palladium(II) (0.051 g, 0.065 mmol), and potassium carbonate (0.45 g, 3.26 mmol) generally according to the procedure described for Intermediate 37 provided 0.404 g (75%) of (±)-[7-(3-chlorophenyl)-2,3-dihydro-l- benzofuran-2-yl] methyl 4-methylbenzenesulfonate as a light yellow solid, mp 101-103 °C; Anal, calcd. for C22H19CIO4S: C, 63.69; H, 4.62. Found: C, 63.59; H, 4.52.

Intermediate 154: (±)-{7-[3-(trifluoromethyl)phenyI]-2,3-dihydro-l-benzofuran -2- yl}methyl 4-methylbenzenesulfonate

Treatment of (±)-(7-bromo-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate (5.0 g, 13.05 mmol) with 3-(trifluoromethyl)phenylboronic acid (3.72 g, 19.57 mmol), dichlorobis(tri-o-tolylphosphine)-palladium(II) (0.512 g, 0.652 mmol), and potassium carbonate (4.5 g, 32.62 mmol) generally according to the procedure described for Intermediate 37 provided 5.28 g (90%) of (±)-{7-[3- (trifluoromethyl)phenyl]-2,3-dihydro-l-benzofuran-2-yl}methy l 4- methylbenzenesulfonate as a white solid, mp 90-93 ⁰ C; Anal, calcd. for C23H19F3O4S: C, 61.6; H, 4.27. Found: C, 61.52; H, 4.21.

Intermediate 155: (±)-benzyl ({7-[3-(trifluoromethyI)phenyl]-2,3-dihydro-l~ benzofuran-2-yl}methyl)carbamate

Treatment of (±)-l-{7-[3-(trifluoromethyl)phenyl]-2,3-dihydro-l-benzofur an-2- yl}methanamine (1.67 g, 5.06 mmol) with diisopropylethylamine (0.98 g, 7.59 mmol) followed by benzyl chloroformate (1.04 g, 7.59 mmol) generally according to the procedure described for Intermediate 12 provided 2.1 g (97%) of (±)-benzyl ({7-[3- (trifluoromethyl)phenyl]-2,3-dihydro-l-benzofuran-2-yl}methy l)carbamate as a colorless oil. Anal, calcd. for C24H20F3NO3: C, 67.44; H, 4.72; N, 3.28. Found: C, 67.08; H, 5.05; N, 3.22. Chiral HPLC separation of (±)-benzyl ({7-[3-(trifluoromethyl)phenyl]-2,3- dihydro-l-benzofuran-2-yl}methyl)carbamate (Chiralpak OJ, isopropanol: carbon dioxide 15:85) provided two fractions. Fraction 1 (R^ = 6.12 min, Chiralpak OJ, isopropanolxarbon dioxide 15:85); Fraction 2 (R^ = 7.17 min, Chiralpak OJ, isopropanolxarbon dioxide 15:85).

Intermediate 156: (±)-[7-(4-methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methy l 4- methylbenzenesulfonate

Treatment of (±)-(7-bromo-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate (11.2 g, 29.22 mmol) with 4-methylphenylboronic acid (5.96 g, 43.84 mmol), dichlorobis(tri-o-tolylphosphine)-ρalladium(II) (1.15 g, 1.46 mmol), and potassium carbonate (10.10 g, 73.07 mmol) generally according to the procedure described for Intermediate 37 provided 9.8 g (85%) of (±)-[7-(4-methylphenyl)-2,3-

dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate as a white solid, mp 145- 147 °C; Anal, calcd. for C23H22O4S: C, 70.03; H, 5.62. Found: C, 69.91; H, 5.7.

Intermediate 157: (±)-benzyl {[7-(4-methylphenyl)-2,3-dihydro-l-benzofuran-2- yl]methyl}carbamate

Treatment of (±)- 1 -[7-(4-methylphenyl)-2,3-dihydro- 1 -benzofuran-2- yljmethanamine (5.8 g, 24.24 mmol) with diisopropylethylamine (4.69 g, 36.35 mmol) followed by benzyl chloroformate (5.17 g, 30.30 mmol) generally according to the procedure described for Intermediate 12 provided 5.05 g (56%) of (±)-benzyl {[7-(4- methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}carbamate as a clear oil. Anal, calcd. for C24H23NO3: C, 77.19; H, 6.21; N, 3.75. Found: C, 76.97; H, 5.99; N, 3.68.

Chiral HPLC separation of (±)-benzyl {[7-(4-methylphenyl)-2,3-dihydro-l-benzofuran-2- yl]methyl} carbamate (Chiralpak OD, methanol: carbon dioxide 1:1) provided two fractions. Fraction 1 (Rf = 3.735 min, Chiralpak OD, methanol: carbon dioxide 1:1); Fraction 2 (R^ = 4.381 min, Chiralpak OD ₃ methanol: carbon dioxide 1:1).

Intermediate 158: (±)-[7-(4-fluorophenyl)-2,3-dihydro-l-benzofuran-2-yI] methyl 4- methylbenzenesulfonate

Treatment of (±)-(7-bromo-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate (0.50 g, 1.305 mmol) with 4-fluorophenylboronic acid (0.274 g, 1.96 mmol), dichlorobis(tri-o-tolylphosphine)-palladium(II) (0.051 g, 0.065 mmol), and potassium carbonate (0.45 g, 3.26 mmol) generally according to the procedure described for Intermediate 37 provided 0.408 g (78%) of (±)-[7-(4-fluorophenyl)-2,3-dihydro-l- benzofuran-2-yl]methyl 4-methylbenzenesulfonate as a light yellow solid, mp 83-86 ⁰ C; Anal, calcd. for C22H19FO4S: C, 66.32; H, 4.81. Found: C, 66.11; H, 4.61.

Intermediate 159: (±)-[7-(4-chlorophenyl)-2,3-dihydro-l-benzofuran-2-yI] methyl 4- methylbenzenesulfonate

Treatment of (±)-(7-bromo-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate (0.50 g, 1.305 mmol) with 4-chlorophenylboronic acid (0.306 g, 1.96 mmol), dicUorobis(tri-o-tolylphosphine)-palladium(II) (0.051 g, 0.065 mmol), and potassium carbonate (0.45 g, 3.26 mmol) generally according to the procedure described

for Intermediate 37 provided 0.367 g (68%) of (±)-[7-(4-chlorophenyl)-2,3-dihydro-l- benzofuran-2-yl] methyl 4-methylbenzenesulfonate as an orange solid, mp 130-133 °C; Anal, calcd. for C22H19CIO4S: C ₅ 63.69; H, 4.62. Found: C, 62.82; H, 4.56.

Intermediate 160: (±)-{7-[4-(trifluoromethyl)phenyI]-2,3-dihydro-l-benzofuran -2- yl}methyl 4-methylbenzenesulfonate

Treatment of (±)-(7-bromo-2,3-dihydro-l-benzofuran-2-yl)m ethyl A- methylbenzenesulfonate (0.50 g, 1.305 mmol) with 4-(trifluoromethyl)phenylboronic acid (0.372 g, 1.96 mmol), dichlorobis(tri-o-tolylphosphine)-palladium(II) (0.051 g, 0.065 mmol), and potassium carbonate (0.45 g, 3.26 mmol) generally according to the procedure described for Intermediate 37 provided 0.435 g (74%) of (±)-{7-[4- (trifluoromethyl)phenyl]-2,3-dihydro-l-benzofuran-2-yl}methy l 4- methylbenzenesulfonate as a light yellow solid, mp 116-118 ⁰ C; Anal, calcd. for C23H19F3O4S: C, 61.6; H, 4.27. Found: C, 61.37; H, 4.36.

Intermediate 161: (±)-[7-(2,6-dimethylphenyl)-2,3-dihydro-l-benzofuran~2- yl]methyl 4-methylbenzenesulfonate

Treatment of (±)-(7-bromo-2,3-dihydro-l-benzofuran-2-yl)methyl A- methylbenzenesulfonate (1.0 g, 2.61 mmol) with 2,6-dimethylphenylboronic acid (0.783 g, 5.22 mmol), dichlorobis(tri-o-tolylphosphine)-palladium(II) (0.103 g, 0.131 mmol), and potassium carbonate (0.902 g, 6.52 mmol) generally according to the procedure described for Intermediate 37 provided 0.192 g (18%) of (±)-[7-(2,6-dimethylphenyl)-2,3- dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate as a yellow oil. Anal, calcd. for C24H24O4S: C, 70.56; H, 5.92. Found: C, 68.01; H, 5.6.

Intermediate 162: (±)-benzyl {[7-(2,6-dimethylphenyl)-2,3-dihydro-l-benzofuran-2- yl]methyl}carbamate

Treatment of (±)-l-[7-(2,6-dimethylphenyl)-2,3-dihydro-l-benzofuran-2- yl]methanamine (0.947 g, 3.73 mmol) with diisopropylethylamine (0.725 g, 5.60 mmol) followed by benzyl chloroformate (0.765 g, 4.48 mmol) generally according to the procedure described for Intermediate 12 provided 1,26 g (87%) of (±)-benzyl {[7-(2,6- dimethylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl} carbamate as a colorless oil.

Anal, calcd. for C25H25NO3: C, 77.49; H, 6.5; N, 3.61. Found: C, 77.42; H, 6.57; N,

3.62. Chiral HPLC separation of (±)-benzyl {[7-(2,6-dimethylphenyl)-2,3-dihydro-l- benzofuran-2-yl]methyl}carbamate (Chiralcel OJ, methanol: carbon dioxide 4:6) provided two fractions. Fraction 1 (R^ = 3.12 min, Chiralcel OJ, methanol: carbon dioxide 4:6); Fraction 2 (R _t = 4.28 min, Chiralcel OJ methanol: carbon dioxide 4:6).

Intermediate 163: 2',6'-difluoro-l,l'-biphenyl-2-ol

Treatment of 2,6-difluorobromobenzene (8.9 g, 46.1 mmol) with 2- methoxybenzeneboronic acid (10.51 g, 69.2 mmol), dichlorobis(tri-o-tolylphosphine)- palladium(II) (1.81 g, 2.3 mmol), and potassium carbonate (15.9 g, 115.3 mmol) generally according to the procedure described for Intermediate 37 provided 4.6 g (45%) of 2',6'-difluoro-l,r-biphenyl-2-yl methyl ether. To a solution of 2',6'-difluoro-l,l'- biphenyl-2-yl methyl ether (4.5 g, 20.4 mmol) in dichloromethane (100 mL) cooled to - 78 °C was added boron tribromide (5.11 g, 1.0 M in dichloromethane) and the reaction mixture was allowed to stir for 30 min. The reaction mixture was allowed to warm to room temperature and was quenched by the addition of ice (150 mL). The organic layer was separated and the aqueous layer was extracted with dichloromethane (500 mL). The combined organic layers were washed with water (400 mL), saturated aqueous sodium chloride (100 mL), dried (magnesium sulfate), and the solvent removed in vacuo to provide a crude oil. Purification by flash column chromatography (silica, hexanes:ethyl acetate 95:5) provided 3.95 g (94%) of 2',6'-difluoro-l, l'-biphenyl-2-ol as a colorless oil. Anal, calcd. for C ₁₂ H ₈ F ₂ O: C, 69.9; H, 3.91. Found: C, 68.51; H, 4.06.

Intermediate 164: (±)-[7-(2,6-difluorophenyl)-2,3-dihydro-l-benzofuran~2- yl]methanol

Treatment of 2',6'-difluoro- l,l'-biphenyl-2-ol (3.8 g, 18.43 mmol) with potassium carbonate (10.19 g, 73.72 mmol) and allyl bromide (2.67 g, 22.11 mol), followed by refluxing the resultant allyl ether in mesitylene generally according to the procedure described for Intermediate 8 provided 3-allyl-2 ^l ,6'-difluoro-l,r-biphenyl-2-ol. Treatment of the 3-allyl-2 ^l ,6 ^l -difluoro-l,l'-biphenyl-2-ol (3.41 g, 13.85 mmol) with 3- chloroperoxybenzoic acid (7.25 g, 41.54 mmol, 77%) followed by potassium carbonate (4.78 g, 34.62 mmol) generally according to the procedure described for Intermediate 9

afforded 3.5 g (72%) of (±)-[7-(2,6-difluorophenyl)-2,3-dihydro-l-benzofuran-2- yl]methanol as an amber oil. Anal, calcd. for Ci5Hi ₂ F ₂ O ₂ : C ₅ 68.7; H, 4.61. Found C,

67.26; H, 4.5.

Intermediate 165: (±)-benzyl {[7-(2,6-difluorophenyl)-2,3-dihydro-l-benzofuran-2- yl]methyl}carbamate

Treatment of (±)- 1 - [7-(2,6-difluorophenyl)-2,3 -dihydro- 1 -benzofuran-2- yl]methanamine (1.54 g, 5.17 mmol) with diisopropylethylamine (1.02 g, 7.76 mmol) and benzyl chloroformate (0.971 g, 5.69 mmol) generally according to the procedure described for Intermediate 12 gave 2.02 g (98%) of (±)-benzyl { [7-(2,6~difluorophenyl)- 2,3-dihydro-l-benzofuran-2-yl]methyl}carbamate as a colorless oil. Anal, calcd. for C23H19F2NO3: C, 69.87; H, 4.84; N, 3.54. Found C, 69.54; H, 4.87; N, 3.31.

Intermediate 166: 2',6'-dichIoro-l,l'-biphenyl-2-oI Treatment of 2,6-dichlorobromobenzene (25.0 g, 0.110 mol) with 2- methoxybenzeneboronic acid (25.22 g, 0.166 mol), dichlorobis(tri-o-tolylphosphine)- palladium(II) (2.33 g, 2.96 mmol), and potassium carbonate (34.15 g, 0.247 mmol) generally according to the procedure described for Intermediate 37 provided 21.5 g (77%) of 2',6'-dichloro-l,l'-biρhenyl-2-yl methyl ether. Treatment of 2',6'-dichloro- 1 , 1 '- biphenyl-2-yl methyl ether (19.0 g, 75.06 mmol) with boron tribromide (18.78 g, 1.0 M in dichloromethane) generally according to the procedure described for Intermediate 163 provided 17.89 g (99%) of 2',6'-dichloro-l,r-biphenyl-2-ol as a light yellow solid, mp 100-103 °C; Anal, calcd. for Ci ₂ HsCl ₂ O: C, 60.28 H, 3.37. Found: C, 60.29; H, 3.13.

Intermediate 167: (±)-[7-(2,6-dichlorophenyl)-2,3-dihydro-l-benzofuran-2- yl]methyl 4-methyIbenzenesulfonate

Treatment of 2 ^r ,6'-dichloro-l,l'-biphenyl-2-ol (17.95 g, 75.06 mmol) with potassium carbonate (41.38 g, 299.43 mmol) and allyl bromide (10.89 g, 90.08 mol), followed by refluxing the resultant allyl ether in mesitylene generally according to the procedure described for Intermediate 8 provided 3-allyl-2',6'-dichloro-l,r-biphenyl-2-ol. Treatment of 3-allyl-2',6 ^p -dichloro-l,l'-biρhenyl-2-ol (16.5 g, 59.10 mmol) with 3- chloroperoxybenzoic acid (30.59 g, 177.3 mmol, 77%) followed by potassium carbonate

(20.41 g, 14.77 mmol) generally according to the procedure described for Intermediate 9 afforded 11.2 g (64%) of (±)-[7-(2,6-dichlorophenyl)-2,3-dihydro-l-benzofuran-2- yl]methanol. Treatment of (±)-[7-(2,6-dichlorophenyl)-2,3-dihydro-l -benzofuran-2- yl]methanol (11.2 g, 37.94 mmol) withp-toluenesulfonyl chloride (8.68 g, 45.53 mol) generally according to the procedure described for Intermediate 10 gave 15.2 g (89%) of (±)-[7-(2,6-dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]m ethyl 4- methylbenzenesulfonate as a yellow oil. Anal, calcd. for C22H18CI2O4S: C ₅ 58.8; H,

4.04. Found: C, 58.1; H, 4.05.

Intermediate 168: (±)-benzyl {[7-(2,6-dichlorophenyl)-2,3-dihydro-l-benzofuran-2- yl]methyl}carbamate

Treatment of (±)-l-[7-(2,6-dichlorophenyl)-2,3-dihydro-l-benzofuran-2- yljmethanamine (0.290 g, 0.877 mmol) with diisopropylethylamine (0.170 g, 1.315 mmol) followed by benzyl chloroformate (0.165 g, 0.965 mmol) generally according to the procedure described for Intermediate 12 provided 0.352 g (94%) of (±)-benzyl {[7- (2,6-dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}ca rbamate as a white solid, mp 198-200 °C; Anal, calcd. for C23H19CI2NO3: C, 64.5; H, 4.47; N, 3.27. Found: C,

64.2; H, 4.43; N, 3.21. Chiral HPLC separation of (±)-benzyl {[7-(2,6-dichlorophenyl)- 2,3-dihydro-l-benzofuran-2-yl]methyl} carbamate (Chiralcel AD, ethanol:hexane 1 :1) provided two fractions. Fraction 1 (R^ = 5.174 min, Chiralcel AD, ethanohhexane 1:1);

Fraction 2 (R^ = 6.229 min, Chiralcel AD, ethanohhexane 1 :1).

Intermediate 169: (±)-[7-(2,4-dichlorophenyl)-2,3-dihydro-l-benzofuran-2- yl]methyl 4-methylbenzenesulfonate Treatment of (±)-(7-bromo-2,3-dihydro- 1 -benzofuran-2-yl)methyl A- methylbenzenesulfonate (5.0 g, 13.05 mmol) with 2,4-dichlorophenylboronic acid (3.73 g, 19.57 mmol), dichlorobis(tri-o-tolylphosphine)-palladium(II) (0.512 g, 0.652 mmol), and potassium carbonate (4.51 g, 32.62 mmol) generally according to the procedure described for Intermediate 37 provided 4.5 g (75%) of (±)-[7-(2,4-dichlorophenyl)-2,3- dihydro-l-benzofuran-2-yl]methyl 4-methyIbenzenesulfonate as a yellow oil. Anal, calcd. for C22H18CI2O4S: C, 58.8; H ₅ 4.04. Found: C ₅ 59.01; H, 4.09.

Intermediate 170: (±)-benzyl {[7-(2,4-dichlorophenyl)-2,3-dihydro-l-benzofuran-2- yl]methyl}carbamate

Treatment of (±)-l-[7-(2,4-dichlorophenyl)-2,3-dihydro-l-benzofuran-2- yl]methanamine (1.9 g, 5.75 mmol) with diisopropylethylamine (1.11 g, 8.62 mmol) followed by benzyl chloroformate (1.18 g, 6.89 mmol) generally according to the procedure described for Intermediate 12 gave 2.14 g (87%) of (±)-benzyl {[7-(2,4- dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}carbama te as a white solid, mp 87-89 °C; Anal, calcd. for C23H19CI2NO3: C, 64.5; H, 4.47; N, 3.27. Found: C, 64.65;

H, 4.78; N, 3.08. Chiral HPLC separation of (±)-benzyl {[7-(2,4-dichloroρhenyl)-2,3- dihydro-l-benzofuran-2-yl]methyl}carbamate (Chiralcel AD, methanol: water 95:5) provided two fractions. Fraction 1 (R^ = 8.094 min, Chiralcel AD, methanol: water 95:5);

Fraction 2 (R _t = 9.152 min, Chiralcel AD methanol: water 95:5).

Intermediate 171: (+)-benzyl {[7-(2,4-dichlorophenyl)-2,3-dihydro-l-benzofuran-2- yl] methyl} carbamate

Fraction 1 obtained as a colorless oil from the chiral HPLC separation of (±)- benzyl {[7-(2,4-dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methy l}carbamate (R^ =

8.094 min, Chiralcel AD, methanol: water 95:5). [α]" = +14.36 (c 10.0 in methanol); Anal, calcd. for C ₂ SH ₁₉ Cl ₂ NOs: C, 64.5; H, 4.47; N, 3.27. Found: C, 64.71; H, 4.76; N, 3.34.

Intermediate 172: (-)-benzyl {[7-(2,4-dichIorophenyl)-2,3-dihydro-l-benzofuran-2- yl]methyl}carbamate

Fraction 2 obtained as a colorless oil from the chiral HPLC separation of (±)- benzyl { [7-(2,4-dichlorophenyl)-2,3 -dihydro- 1 -benzofuran-2-yl]methyl } carbamate (R^ =

9.152 min, Chiralcel AD methanol: water 95:5). [α] _t f = -14.66 (c 10.0 in methanol); Anal, calcd. for C ₂₃ H I ₉ Cl ₂ NO ₃ : C, 64.5; H, 4.47; N, 3.27. Found: C, 63.95; H, 4.68; N, 3.27.

Intermediate 173: (±)-[7-(2,4-dimethoxyphenyl)-2,3-dihydro-l-benzofuran-2- yl]methyl 4-methylbenzenesulfonate

Treatment of (±)-(7-bromo-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate (5.0 g, 13.05 mmol) with 2,4-dimethoxyphenylboronic acid (3.56 g, 19.57 mmol), dichlorobis(tri-o-tolylphosphine)-palladium(II) (0.512 g, 0.652 mmol), and potassium carbonate (4.5 g, 32.62 mmol) generally according to the procedure described for Intermediate 37 provided 3.3 g (57%) of (±)-[7~(2,4- dimethoxyphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate as a light yellow solid, mp 120-123 ⁰ C; Anal, calcd. for C24H24O6S: C, 65.44; H, 5.49. Found: C, 64.99; H, 5.46.

Intermediate 174: (±)-benzyl {[7-(2,4-dimethoxyphenyϊ)-2,3-dihydro-l-benzofuran- 2-yl] methyl} carbamate

Treatment of (±)-l -[7-(2,4-dimethoxyphenyl)-2,3-dihydro-l -benzofuran-2- yljmethanamine (1.42 g, 4.41 mmol) with diisopropylethylamine (0.855 g, 6.62 mmol) followed by benzyl chloroformate (0.828 g, 4.85 mmol) generally according to the procedure described for Intermediate 12 provided 1.58 g (85%) of (±)-benzyl {[7-(2,4- dimethoxyphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}carbam ate as a colorless oil. Anal, calcd. for C25H25NO5: C, 71.58; H, 6.01; N ₅ 3.34. Found: C, 71.24; H, 5.92; N, 3.09. Chiral HPLC separation of (±)-benzyl { [7-(2,4-dimethoxyphenyl)-2,3-dihydro-l - benzofuran-2-yl] methyl} carbamate (Chiralcel OD, ethanol) provided two fractions. Fraction 1 (R^ = 5.107 min, Chiralcel OD, ethanol); Fraction 2 (R _t = 6.134 min, Chiralcel

OD, ethanol).

Intermediate 175: (+)-benzyl {[7-(2,4-dimethoxyphenyl)-2,3-dihydro-l-benzofuran- 2-yl] methyl} carbamate

Fraction 1 obtained as a colorless oil from the chiral HPLC separation of (±)- benzyl { [7-(2,4-dimethoxyphenyl)-2,3 -dihydro- 1 -benzofuran-2-yl]rnethyl } carbamate (R^

= 5.107 min, Chiralcel OD, ethanol). [αβ ⁵ = +21.96 (c 10.0 in methanol); Anal, calcd. for C25H25NO5: C, 71.58; H, 6.01; N, 3.34. Found: C, 70.12; H, 6.11; N, 3.12.

Intermediate 176: (-)-benzyl {[7-(2,4-dimethoxyphenyl)-2,3-dib.ydro-l-benzofuran- 2-yl]methyl}carbamate

Fraction 2 obtained as a colorless oil from the chiral HPLC separation of (±)- benzyl { [7-(2,4-dimethoxyphenyl)-2,3 -dihydro- 1 -benzofuran-2-yl]methyl } carbamate (R^ = 6.134 min, Chiralcel OD, ethanol). [α]| ⁵ = -23.20 (c 10.0 in methanol); Anal, calcd. for C25H25NO5: C, 71.58; H, 6.01; N, 3.34. Found: C, 70.22; H, 6.1; N, 3.28.

Intermediate 177: (±)-[7-(2,4-difluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]m ethyl 4-methylbenzenesuIfonate Treatment of (±)-(7-bromo~2,3 -dihydro- 1 -benzofuran-2-yl)methyl 4- methylbenzenesulfonate (5.0 g, 13.05 mmol) with 2,4-difluorophenylboronic acid (3.09 g, 19.57 mmol), dichlorobis(tri-o-tolylphosphine)-palladium(II) (0.512 g, 0.651 mmol), and potassium carbonate (4.51 g, 32.62 mmol) generally according to the procedure described for Intermediate 37 afforded 4.43 g (82%) of (±)-[7-(2,4-difluorophenyl)-2,3-dihydro-l- benzofuran-2-yl]methyl 4-methylbenzenesulfonate as a white solid, mp 116-118 ⁰ C; Anal, calcd. for C22H18F2O4S: C, 63.45; H, 4.36. Found: C, 63.3; H, 4.11.

Intermediate 178: (±)-benzyl {[7-(2,4-difluorophenyl)-2,3-dihydro-l-benzofuran-2- yl]methyl}carbamate Treatment of (±)-l-[7-(2,4-difluorophenyl)-2,3-dihydro-l-benzofuran-2- yljmethanamine (2.0 g, 6.72 mmol) with diisopropylethylamine (1.30 g, 10.07 mmol) followed by benzyl chloroformate (1.26 g, 7.37 mmol) generally according to the procedure described for Intermediate 12 gave 2.14 g (81%) of (±)-benzyl {[7-(2,4- difluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}carbama te as a white solid, mp 78-80 ⁰ C; Anal, calcd. for C23H19F2NO3: C ₅ 69.87; H, 4.84; N, 3.54. Found: C, 69.76;

H, 4.8; N, 3.35. Chiral HPLC separation of (±)-benzyl {[7-(2,4-difluoroρhenyl)-2,3- dihydro-l-benzofuran-2-yl]methyl} carbamate (Chiralpak AD, ethanol :hexane 1 :1) provided two fractions. Fraction 1 (R _t = 9.117 min, Chiralpak AD, ethanol :hexane 1 :1);

Fraction 2 (R^ = 9.424 min, Chiralpak AD ethanol :hexane 1 :1).

Intermediate 179: (+)-benzyl {[7-(2,4-difluorophenyl)-2,3-dihydro-l-benzofuran-2- yl]methyl}carbamate

Fraction 1 obtained as a colorless oil from the chiral HPLC separation of (±)- benzyl {[7-(2,4-difluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methy l}carbamate (R^ = 9.117 min, Chiralpak AD, ethanol:hexane 1 :1). [α]" = +13.0 (c 10.0 in methanol); Anal, calcd. for C23H19F2NO3: C, 69.87; H, 4.84; N, 3.54. Found: C, 69.28; H, 5.23; N, 3.47.

Intermediate 180: (-)-benzyl {[7-(2,4-difluorophenyl)-2,3-dihydro-l-benzofuran-2- yl]methyl}carbamate Fraction 2 obtained as a colorless oil from the chiral HPLC separation of (±)- benzyl {[7-(2,4-difluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methy l} carbamate (R^ =

9.424 min, Chiralpak AD ethanohhexane 1 :1). [α]o = -13.68 (c 10.0 in methanol); Anal, calcd. for C23H19F2NO3: C, 69.87; H, 4.84; N ₃ 3.54. Found: C, 69.65; H, 5.06; N, 3.57.

Intermediate 181: 4'-chloro-2'-methyl-l,l'-biphenyl-2-ol

Treatment of 2-bromo-5-chlorotoluene (5.0 g, 24.33 mmol) with 2- methoxybenzeneboronic acid (4.8 g, 31.63 mmol), dichlorobis(tri-o-tolylρhosphine)- palladium(II) (0.478 g, 0.608 mmol), and potassium carbonate (8.41 g, 60.83 mmol) generally according to the procedure described for Intermediate 37 provided 5.05 g (89%) of 4'-chloro-2'-methyl- 1 , 1 -biphenyl-2-yl methyl ether. Treatment of 4'-chloro-2'-methyl- l,l'-biphenyl-2-yl methyl ether (5.05 g, 21.48 mmol) with boron tribromide (5.37 g, 1.0 M in dichloromethane) generally according to the procedure described for Intermediate 163 provided 4.58 g (97%) of 4'-chloro-2'-methyl-l,l'-biphenyl-2-ol as a yellow oil. Anal, calcd. for C ₁₃ H _{1 1} ClO: C, 71.4; H, 5.07. Found: C, 71.03; H, 4.84.

Intermediate 182: (±)-[7-(4-chloro-2-methylphenyI)-2,3-dihydro-l-benzofuran-2 - yl] methanol

Treatment of 4 ^l -chloro-2'-methyl-l,l'-biphenyl-2-ol (4.54 g, 20.78 mmol) with potassium carbonate (11.47 g, 83.04 mmol) and allyl bromide (3.01 g, 24.91 mol), followed by refluxing the resultant allyl ether in mesitylene generally according to the procedure described for Intermediate 8 provided 3-allyl-4'-chloro-2'-methyl-l,r-

biphenyl-2-ol. Treatment of S-allyW-chloro^'-methyl-U'-biphenyl^-ol (4.5 g, 17.39 mmol) with 3-chloroperoxybenzoic acid (12.0 g, 69.57 mmol, 77%) followed by potassium carbonate (6.0 g, 43.48 mmol) generally according to the procedure described for Intermediate 9 afforded 2.9 g (61%) of (±)-[7-(4-chloro-2-methylphenyl)-2,3-dihydro- l-benzofuran-2-yl]methanol as a colorless oil. Anal, calcd. for C^H^CIC^'- C, 69.95; H, 5.5. Found: C, 69.23; H, 5.42.

Intermediate 183: (±)-[7-(4-chIoro-2-methyIphenyl)-2,3-dihydro-l-benzofuran-2 - yljmethyl 4-methylbenzenesulfonate Treatment of (±)-[7-(4-chloro-2-methylphenyl)-2,3-dihydro-l -benzofuran-2- yljmethanol (2.78 g, 10.11 mmol) withp-toluenesulfonyl chloride (2.31 g, 12.14 mol) generally according to the procedure described for Intermediate 10 gave 4.04 g (93%) of (±)- [7-(4-chloro-2-methylphenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methyl 4- methylbenzenesulfonate as a yellow oil. Anal, calcd. for C23H21CIO4S: C, 64.4; H, 4.93. Found: C, 64.24; H, 4.93.

Intermediate 184: No compound.

Intermediate 185: (+) -[~7-bromo-2,3-dihydro-l-benzofuran-2-yl]methyI 4- methylbenzenesulfonate

Fraction 1 obtained as a white solid from the chiral HPLC separation of 7-bromo- 2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (R^ = 6.220 min,

Chiraicel AD ₅ ethanol). [α]" = +23.4 (c 10.0 in methanol); mp 96-99 °C.

Intermediate 186: (~)-[-7-bromo-2,3-dihydro-l-benzofuran-2-yl]methyl 4- methylbenzenesulfonate

Fraction 2 obtained as a white solid from the chiral HPLC separation of 7-bromo- 2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (R/ = 6.220 min,

Chiraicel AD, ethanol). [α]^ ⁵ = -22.00 (c 10.0 in methanol); mp 96-99 °C.

Intermediate 187: (±)-[7-(2,3-dimethylphenyl)-2,3-dihydro-l-benzofuran-2- yl] methyl 4-methylbenzenesulf onate

Treatment of (±)-(7-bromo-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate (0.50 g, 1.305 mmol) with (2,3-dimethylphenyl)boronic acid (0.294 g, 1.96 mmol) generally according to the procedure described for Intermediate 184 provided 0.335 g (62%) of (±)-[7-(2,3-dimethylρhenyl)-2,3-dihydro-l-benzofuran-2- yljmethyl 4-methylbenzenesulfonate as a white solid. Rf= 0.43 (silica, ethyl acetate :hexanes 1 :4).

Intermediate 188: (±)-[7-(2,3-dimethoxyphenyl)-2,3-dihydro-l-benzofuran-2- y I] methyl 4-methylbenzenesulfonate

Treatment of (±)-(7-bromo-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate (0.30 g, 0.783 mmol) with (2,3-dimethoxylphenyl)boronic acid (0.427 g, 2.35 mmol) generally according to the procedure described for Intermediate 184 provided 0.283 g (82%) of (±)-[7-(2,3-dimethoxylphenyl)-2,3-dihydro-l-benzofuran-2- yljmethyl 4-methylbenzenesulfonate as a white solid. R^= 0.43 (silica, ethyl acetate :hexanes 1 :4).

Intermediate 189: (±)-[7-(2,3-difluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]m ethyl 4-methylbenzenesulfonate

Treatment of (±)-(7-bromo-2,3-dihydro-l-benzofuran-2-yl)m ethyl 4- methylbenzenesulfonate (0.50 g, 1.305 mmol) with (2,3-difluorophenyl)boronic acid (0.618 g, 3.91 mmol) generally according to the procedure described for Intermediate 184 provided 0.090 g (77%) of (±)-[7-(2,3-difluorophenyl)-2,3-dihydro-l-benzofuran-2- yl]methyl 4-methylbenzenesulfonate as a white solid. Rf= 0.43 (silica, ethyl acetate :hexanes 1:4).

Intermediate 190: (±)-[7-(2,5-dimethylphenyl)-2,3-dihydro-l-benzofuran-2- yljmethyl 4-methylbenzenesulfonate Treatment of (±)-(7-bromo-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate (0.50 g, 1.305 mmol) with (2,5-dimethylphenyl)boronic acid (0.294 g, 1.96 mmol) generally according to the procedure described for Intermediate 184

provided 0.430 g (81%) of (±)-[7-(2,5-dimethylρhenyl)-2,3-dihydro-l-benzofuran-2- yl]methyl 4-methylbenzenesulfonate as a white solid. Rf= 0.43 (silica, ethyl acetate:hexanes 1:4).

Intermediate 191: (±)-[7-(2,5-difluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]m ethyl 4-methylbenzenesulfonate

Treatment of (±)-(7-bromo-2,3-dihydro-l-benzofuran-2-yl)methyl A- methylbenzenesulfonate (0.50 g, 1.305 mmol) with (2,5-difluorophenyl)boronic acid (0.309 g, 1.96 mmol) generally according to the procedure described for Intermediate 184 provided 0.360 g (66%) of (±)-[7-(2,3-difluorophenyl)-2,3-dihydro-l-benzofuran-2- yljmethyl 4-methylbenzenesulfonate as a white solid. Rf= 0.43 (silica, ethyl acetate :hexanes 1 :4).

Intermediate 192: [7-(2,5-dichIorophenyl)-2,3-dihydro-l-benzofuran-2-yl] methyl 4- methylbenzenesulfonate

Treatment of (±)-(7-bromo-2,3-dihydro-l-benzofuran-2-yl)methyl A- methylbenzenesulfonate (1.43 g, 3.73 mmol) with (2,5-dichlorophenyl)boronic acid (1.07 g, 5.59 mmol) generally according to the procedure described for Intermediate 184 provided 1.49 g (88%) of (±)[7-(2,5-dichlorophenyl)-2,3-dihydro-l-benzofuran-2- yl]methyl 4-methylbenzenesulfonate as a white solid. Rf= 0.43 (silica, ethyl acetate:hexanes 1 :4.

Intermediate 193: (±)-[7-(2,5-dimethoxyphenyl)-2,3-dihydro-l-benzofuran-2- yl]methyl 4-methylbenzenesulfonate Treatment of (±)-(7-bromo-2,3-dihydro- 1 -benzofuran-2-yl)methyl A- methylbenzenesulfonate (0.50 g, 1.305 mmol) with (2,5-dimethoxyphenyl)boronic acid (0.356 g, 1.96 mmol) generally according to the procedure described for Intermediate 184 provided 0.291 g (51%) of (±)-[7-(2,5-dimethoxyphenyl)-2,3-dihydro-l-benzofuran-2- yl]methyl 4-methylbenzenesulfonate as a white solid. 0.43 (silica, ethyl acetate :hexanes 1:4).

Intermediate 194: (±)-[7-(5-chloro-2-methyIphenyI)-2,3-dihydro-l-benzofuran-2 - yl]methyI 4-methylbenzenesulfonate

Treatment of (±)-(7-bromo-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate (0.50 g, 1.305 mmol) with (5-chloro-2-methylphenyl)boronic acid (0.334 g, 1.96 mmol) generally according to the procedure described for

Intermediate 184 provided 0.451 g (81%) of (±)-[7-(5-chloro-2methylphenyl)-2,3- dihydro-l-benzofuran-2-yl] methyl 4-methylbenzenesulfonate as a white solid. Rf= 0.43

(silica, ethyl acetate :hexanes 1:4).

Intermediate 195: (±)-[7-(5-chloro-2-methoxyphenyI)-2,3-dihydro-l-benzofuran- 2- yl] methyl 4-methylbenzenesulfonate

Treatment of (±)-(7-bromo-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate (0.50 g, 1.305 mmol) with (5-chloro-2-methoxyphenyl)boronic acid (0.365 g, 1.96 mmol generally according to the procedure described for Intermediate 184 provided 0.382 g (66%) of (±)-[7-(5-chloro-2-methoxyphenyl)-2,3-dihydro-l- benzofuran-2-yl]methyl 4-methylbenzenesulfonate as a white solid. Rf= 0.43 (silica, ethyl acetate :hexanes 1 :4).

Intermediate 196: (±)-[7-(2,4,6-trichIorophenyl)-2,3-dihydro-l-benzofuran-2- yl]methyl 4-methylbenzenesulfonate

Treatment of 2,4,6-trichlorobromobenzene (14.5 g, 55.69 mmol) with 2- methoxybenzeneboronic acid (12.69 g, 83.54 mol), dichlorobis(tri-o-tolylphosphine)- palladium(II) (0.656 g, 0.835 mmol), and potassium carbonate (19.21 g, 139.22 mmol) generally according to the procedure described for Intermediate 37 provided 9.8 g (61%) of 2' 4 ^l ,6'-trichloro-l,l'-biphenyl-2-yl methyl ether. To a solution of 2' 4',6'-trichloro-l,r- biphenyl-2-yl methyl ether (9.8 g, 34.08 mmol) in dichloromethane (100 mL) cooled to - 78 ⁰ C was added boron tribromide (9.38 g, 1.0 M in dichloromethane) generally according to the procedure described for Intermediate 163 provided provided 9.2 g of a yellow solid. Treatment of 2',4',6 ^l -trichloro-l ₅ l'-biρhenyl-2-ol (9.17 g, 33.52 mmol) with potassium carbonate (18.53 g, 134.1 mmol) and allyl bromide (4.46 g, 36.87 mol), followed by refluxing the resultant allyl ether in mesitylene generally according to the procedure described for Intermediate 8 provided 3-allyl-2^4',6'-trichloro-l,r-biphenyl-2-

ol. Treatment of 3-allyl-2',4',6'-trichloro-l,r-biρhenyl-2-ol. (10.35g, 33.00 mmol) with 3-chloroperoxybenzoic acid (17.08 g, 99.00 mmol, 77%) followed by potassium carbonate (11.40 g, 82.51 mmol) generally according to the procedure described for Intermediate 9 afforded 10.4 g (95%) of (±)-[7-(2,4,6-trichlorophenyl)-2,3-dihydro-l- benzofuran-2-yl]methanol. Treatment of (±)-[7-(2,4,6-trichlorophenyl)-2,3-dihydro-l - benzofuran-2-yl]methanol (10.38 g, 31.49 mmol) withjσ-toluenesulfonyl chloride (7.20 g, 37.79 mol) generally according to the procedure described for Intermediate 10 gave 10.5 g (68%) of (±)-[7-(2,6-dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]m ethyl 4- methylbenzenesulfonate as a white solid, mp 178-180 ⁰ C.

Intermediate 197: (±)-(7~pyridin-3-yl-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate

Treatment of (±)-(7-bromo-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate (4.0 g, 10.44 mmol) with pyridin-3-ylboronic acid (3.85 g, 31.31 mmol), tetrakis tri-phenylphosphine palladium (0.362 g, 0.052 mmol), and potassium carbonate (3.61 g, 26.09 mmol) generally according to the procedure described for Intermediate 184 provided 2.47 g (62%) of (±)-(7-pyridin-3-yl-2,3-dihydro-l- benzofuran-2-yl)methyl 4-methylbenzenesulfonates a light yellow solid. Ry= 0.43 (silica, ethyl acetate:hexanes 1 :4).

Intermediate 198: (±)-(7-nitro-2,3-dihydro-l-benzofuran-2-yI)methanol

To a solution of 2-nitrophenol (13.9 g, 100 mmol) in λζiV-dimethylformamide (300 mL) was added with sodium hydride (4.2 g, 100 mmol 60%) followed by allyl bromide (13.3 g, 110 mmol) and the reaction was allowed to stir at room temperature for 2 hours The reaction mixture was diluted with water (500 mL) to dissolve any solids and extracted with ethyl acetate (3 x 250 mL). The combined organic layers were washed with water (4 x 500 mL), saturated aqueous sodium chloride (400 mL), dried (magnesium sulfate) and the solvent removed in vacuo to give 1 -(allyl oxy)-2-nitrobenzene. The oil was re-dissolved in mesitylene (500 mL) and heated at reflux for 3 d. Removal of the solvent in vacuo provided a crude oil. Purification by flash column chromatography

(silica, dichloromethane:hexanes 0.5:9.5) provided 6.8 g, (50%) of 2-allyl-6-nitrophenol as a yellow oil. To a solution of 2-allyl-6-nitrophenol (6.6 g, 36.84 mmol) in

dichloromethane (300 mL) was added 3-chloroperoxybenzoic acid (77%, 16.5 g, 73.67 mmol) The reaction mixture was allowed to stir at room temperature for 8 h. The reaction mixture was washed with a 1 :1 solution of 10% sodium sulfite: saturated sodium bicarbonate (2 x 300 mL). The solvent was removed in vacuo to give crude yellow oil. The oil was diluted with methanol (300 mL) and added to a solution of potassium carbonate (15.0 g, 108.5 mmol) the solution was allowed to stir at room temperature 2 h. The solvent was removed in vacuo. The residue was washed with water (1000 mL) and ethyl acetate (500 mL). The aqueous layer was acidified with 1 N aqueous hydrogen chloride and washed with ethyl acetate (500 mL). The combined organics were washed with water (500 mL), saturated aqueous sodium chloride (500 mL), dried (magnesium sulfate) and the solvent removed in vacuo to provide a crude solid. Purification by flash column chromatography (silica, dichloromethane :hexanes 4:10) provided 3.18 g (44%) of (±)-(7-nitro-2,3-dihydro-l-benzofuran-2-yl)methanol as yellow solid, mp 63-65 °C.

Intermediate 199: (±)-(7-nitro-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate

To a solution of (±)-(7-nitro-2,3-dihydro-l-benzofuran-2-yl)methanol (3.14 g, 16.09 mol) in dichloromethane (100 mL) was added diisopropylethyl amine (4.16 g, 32.18 mmol), N,N-dimethylaminopyridine (0.39 g, 3.2 mmol), and /?-toluenesulfonyl chloride (4.6 g, 24.13 mmol) the reaction was allowed to stir at room temperature for 12 h. The reaction was diluted with dichloromethane (500 mL), washed with saturated aqueous sodium bicarbonate (200 mL), saturated aqueous sodium chloride (200 mL), dried (magnesium sulfate) and the solvent removed in vacuo to give a crude oil. Purification by flash column chromatography (silica, dichloromethane: hexanes 3:10) afforded 5.2 g (94%) of (±)-(7-nitro-2,3-dihydro- 1 -benzofuran-2-yl)methyl 4- methylbenzenesulfonate as off-white solid, mp 129-131°C.

Intermediate 200: (±)-(7-amino~2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate A solution of (±)-(7-amino-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate (4.8 g, 13.74 mmol) in ethanol (400 mL) and palladium on carbon (1.4 g, 5 wt.%) was shaken under an H2 atmosphere (50 psi) for 12 h. The

reaction mixture was filtered (celite) and the solvent removed in vacuo provided 4.4 g (99%) of (±)-(7-amino-2,3-dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate as a light brown oil.

Intermediate 201: (±)-{7-[(4-methylphenyI)ammo]-2,3-dihydro-l-benzofuran-2- yl}methyl 4-methylbenzenesulfonate

Treatment of (±)-(7-anilino-2,3-dihydro-l-benzofuran-2-yl)methyl A- methylbenzenesulfonate (0.96 g, 3.0 mmol) in toluene (20 mL) with l-bromo-4- methylbenzene (0.513 g, 3.0 mmol)dichloro [1,1'- bis(diphenylphosphino)ferrocene]palladium(II)dichloro-methan e (0.061 g, .075 mmol), l,l '-bis(diphenylphosphino)ferrocene (0.125 g, 0.225 mmol), sodium /ert-butoxide (0.18 g, 1.875 mmol) the reaction was allowed to reflux 3 h. The solvent was removed in vacuo. The residue was washed with water (10OmL) and ethyl acetate (5OmL). The combined organic layers were washed with saturated aqueous sodium chloride, dried (magnesium sulfate), and the solvent removed in vacuo to provide a crude oil. Purification by flash column chromatography (silica, ethyl acetate: hexanes 3:10) afforded 0.36 g (29%) of (±)-{7-[(4-methylphenyl)amino]-2,3-dihydro-l-benzofuran-2- yl}methyl 4-methylbenzenesulfonate as a yellow solid, mp 118-120 ⁰ C.

Intermediate 202: (±)-{7-[(4-chlorophenyI)amino]-2,3-dihydro-l-benzofuran-2- yl}methyl 4-methylbenzenesulfonate

Treatment of (±)-(7-amino-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate (0.96 g, 3.0 mmol) with l-bromo-4-chlorobenzene (0.570 g, 3.0 mmol) generally according to the procedure described for Intermediate 37 provided 0.77 g (57%) of (±)-{7-[(4-chlorophenyl)amino]-2,3-dihydro-l-benzofuran-2-y l}methyl A- methylbenzenesulfonate as a white solid, mp 132-134 °C.

Intermediate 203: (±)-{7-[(3,4-dimethylphenyl)amino]-2,3-dihydro-l-benzofuran -2- yl}methyl 4-methylbenzenesulfonate Treatment of (±)-(7-amino-2,3-dihydro- 1 -benzofuran-2-yl)methyl A- methylbenzenesulfonate (0.96 g, 3.0 mmol) with 4-bromo-l,2-dimethylbenzene

(0.558 g, 3.0 mmol), generally according to the procedure described for Intermediate 202 provided 0.51 g (38%) (±)-{7-[(3,4-dimethylphenyl)amino]-2,3-dihydro-l-benzofuran -2- yl}methyl 4-methylbenzenesulfonate as a yellow solid, mp 88-90 °C.

Intermediate 204: (±)-benzyl {[7-(2,3-dimethoxyphenyl)-2,3-dihydro-l-benzofuran- 2-yI] methyljcarbamate

Treatment of (±)-benzyl [7-(2,3 -dimethoxyphenyl)-2,3 -dihydro- 1 -benzofuran-2- yl] methanamine (2.7 g, 8.39 mmol) with diisopropylethylamine (1.63 g, 12.59 mmol) and benzyl chloroformate (1.72 g, 10.07 mmol) generally according to the procedure described for Intermediate 12 provided 3.21 g (91 %) of (±)-benzyl { [7-(2,3- dimethoxyphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}carbam ate as a colorless oil.

Intermediate 205: (±)-benzyl {[7-(4-chloro-2-methylphenyl)-2,3-dihydro-l- benzofuran-2-yl]methyl}carbamate Treatment of (±)-benzyl [7-(4-chloro-2-methylphenyl)-2,3 -dihydro- 1 -benzofuran-

2-yl] methanamine (0.979 g, 3.15 mmol) with diisopropylethylamine (0.612 g, 4.73 mmol) and benzyl chloroformate (0.646 g, 3.79 mmol) generally according to the procedure described for Intermediate 12 provided 1.2 g (96%) of (±)-benzyl [7-(4-chloro- 2-methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]carbamate as a colorless oil.

Intermediate 206: (+)-benzyl {[7-(4-chIoro-2-methylphenyI)-2,3-dihydro-l- benzofuran-2-yl]methyl}carbamate

Fraction 1 obtained as a colorless oil from the chiral HPLC separation of (±)- benzyl [7-(2,3-dimethoxyphenyl)-2,3-dihydro-l-benzofuran-2-yl]carba mate (R^ = 7.725 min, Chiralcel AD, ethanol:hexane 1 : 1). [α]^ ⁵ = +12.8 (c 10.0 in methanol).

Intermediate 207: (-)-benzyl {[7-(4-chloro-2-methylphenyl)-2,3-dihydro-l- benzofuran-2-yl]methyl}carbamate

Fraction 2 obtained as a colorless oil from the chiral HPLC separation of (±)- benzyl [7-(2 ₅ 3-dimethoxyphenyl)-2,3-dihydro-l-benzofuran-2-yl]carbamate (R _t = 9.542 min, Chiralcel AD ₅ ethanohhexane 1 :1). [α]p ⁵ = -4.8 (c 10.0 in methanol).

Intermediate 208: (+)-benzyl {[7-(2,6-difluorophenyI)-2,3-dihydro-l-benzofuran-2- yl]methyl}carbamate

Fraction 1 obtained as a colorless oil from the chiral HPLC separation of (±)- benzyl [7-(2,6-difluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]carbam ate (R^ = 4.340 min, Chiralcel AD, isopropanol:hexane 2:8). [α]^ ⁵ = +18.8 (c 10.0 in methanol).

Intermediate 209: (-)-benzyl {[7~(2,6-difluorophenyI)-2,3-dihydro-l-benzofuran-2- y 1] methyl} carb amate

Fraction 2 obtained as a colorless oil from the chiral HPLC separation of (±)- benzyl [7-(2,6-difluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]carbam ate (R^ = 5.251 min, Chiralcel AD, isopropanol:hexane 2:8). [α]^ ⁵ = -16.8 (c 10.0 in methanol).

Intermediate 210: (±)-benzyl {[7-(5-chloro-2-methylphenyl)-2,3-dihydro-l- benzofuran-2-yl]methyI}carbamate Treatment of (±)-benzyl [7-(4-chloro-2-methylphenyl)-2,3-dihydro- 1 -benzofuran-

2-yl] methanamine (3.1 g, 11.32 mmol) with diisopropylethylamine (2.19 g, 16.98 mmol) and benzyl chloroformate (2.37 g, 12.45 mmol) generally according to the procedure described for Intermediate 12 provided 4.12 g (89%) of (±)-benzyl {[7-(5-chloro-2- methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}carbamate as a colorless oil.

Intermediate 211: (±)-benzyl {[7-(2,4,6-trichlorophenyI)-2,3-dihydro-l-benzofuran- 2-yl] methyljcarbamate

Treatment of (±)-benzyl [7-(2,4,6-trichlorophenyl)-2,3-dihydro-l -benzofuran-2- yl] methanamine (2.83 g, 8.61 mmol) with diisopropylethylamine (1.67 g, 12.92 mmol) and benzyl chloroformate (1.76 g, 10.33 mmol) generally according to the procedure described for Intermediate 12 provided 3.46 g (87%) of (±)-benzyl {[7-(2,4,6- trichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl} carbamate as a colorless oil.

Intermediate 212: (±)-benzyI [(7-pyridin-3-yl-2,3-dihydro-l-benzofuran-2- yl)m ethyl] carbamate

Treatment of (±)- 1 -(7-pyridin-3 -yl-2,3 -dihydro- 1 -benzofuran-2-yl)methanamine

(0.770 g, 3.40 mmol) with diisopropylethylamine (0.660 g, 5.1 mmol) and benzyl

chloroformate (0.778 g, 4.08 mmol) generally according to the procedure described for Intermediate 12 provided 0.702 g (57%) of (±)-benzyl [(7-pyridin-3-yl-2,3-dihydro-l- benzofuran-2-yl)methyl]carbamate as an amber oil.

Intermediate 213: (±)-benzyl{[7-(2-chlorophenyl)-2,3-dihydro-l-benzofuran-2- yl]methyl}methylcarbamate

Treatment of (±)-[(N-methyl-l-[7-(2-chlorophenyl)-2,3-dihydro-l-benzofur an-2- yl]methanamine (0.932 g, 3.4 mmol) with diisopropylethylamine (0.66 g, 5.11 mmol) and benzyl chloroformate (0.778 g, 4.08 mmol) generally according to the procedure described for Intermediate 12 provided 1.25 g (86%) of (±)-benzyl { [7-(2-chlorophenyl)- 2,3-dihydro-l-benzofuran-2-yl]methyl}methylcarbamate as a colorless oil.

Intermediate 214: (±)-benzyl{[7-(2-methylphenyl)-2,3-dihydro-l-benzofuran-2- y 1] methyl} methy lcarb amate Treatment of (±)- [(N-methyl- 1 - [7-(2-methylphenyl)-2,3-dihydro- 1 -benzofuran-2- yl]methanamine (0.67 g, 32.64 mmol) with diisopropylethylamine (0.512 g, 3.97 mmol) and benzyl chloroformate (0.605 g, 3.17 mmol) generally according to the procedure described for Intermediate 12 provided 0.790 g (77%) of (±)-benzyl {[7-(2- methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}methylcar bamate as a colorless oil.

Intermediate 215: (±)-benzyI{[7-(2,6-dichlorophenyl)-2,3-dihydro-l-benzofuran -2- yl]methyl}methylcarbamate

Treatment of (±)-[(N-methyl- 1 -[7-(2,6-dichlorophenyl)-2,3-dihydro- 1 - benzofuran-2-yl]methanamine (1.1 g, 3.57 mmol) with diisopropylethylamine (0.69 g, 5.35 mmol) and benzyl chloroformate (0.0.82 g, 4.28 mmol) generally according to the procedure described for Intermediate 12 provided 1.6 g (99%) of (±)-benzyl {[7-(2,6- dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}methylc arbamate as a colorless oil.

Intermediate 216: (±)-benzyl{[7-pyridin-3-yl-2,3-dihydro-l-benzofuran-2- yl]methyl}methylcarbamate

Treatment of (±)-(7-bromo-2,3-dihydro-benzofuran-2-ylmethyl)carbamate (0.80 g, 2.21 mmol) with pyridine-3-boronic acid (0.407 g, 3.31 mmol) generally according to the procedure described for Intermediate 37 provided 0.213 g (27%) of (±)-benzyl {[7- pyridine-3-yl-2,3-dihydro-l-benzofuran-2-yl]methyl}methylcar bamate as a colorless oil.

Intermediate 217: (±)-benzyl{[7-(2,3-dichlorophenyl)-2,3-dihydro-l-benzofuran -2- yl]methyl}carbamate Treatment of (±)-(7-bromo-2,3-dihydro-benzofuran-2-ylmethyl)carbamate (1.3 g,

3.59 mmol) with 2,3-dichlorophenylboronic acid (1.03 g, 5.38 mmol) generally according to the procedure described for Intermediate 37 provided 0.93 g (63%) of (±)-benzyl{[7- (2,3-dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methylcar bamate as a yellow oil.

Intermediate 218: (±)-benzyl{[7-(2,5-dichlorophenyI)-2,3-dihydro-l-benzofuran -2- yl]methyl}carbamate

Treatment of (±)-(7-bromo-2,3-dihydro-benzofuran-2-ylmethyl)carbamate (3.2 g, 8.83 mmol) with 2,5-dichlorophenylboronic acid (2.54 g, 13.24 mmol) generally according to the procedure described for Intermediate 37 provided 0.299 g (27%) of (±)- benzyl {[7-(2,5-dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methy l}carbamate as a yellow oil.

Intermediate 219: (±)-benzyl {[7-(2,4,6-trichlorophenyl)-2,3-dihydro-l-benzofuran- 2-yl] methyl} carbamate Treatment of (±)-{ [7-(2,4,6-trichlorophenyl)-2,3-dihydro-l-benzofuran-2- yl]methyl}amine (1.1 g, 3.57 mmol) with diisopropylethylamine (0.69 g, 5.35 mmol) and benzyl chloroformate (0.0.82 g, 4.28 mmol) generally according to the procedure described for Intermediate 12 provided 1.6 g (99%) of (±)-benzyl {[7-(2,4,6- trichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}carbam ate as a colorless oil.

Intermediate 220: (±)-benzyl methyl{[7-(2,4,6-trichlorophenyl)-2,3-dihydro-l- benzofuran-2-yl]methyl}carbamate

Treatment of (±)-iV-methyl-l -[7-(2,4,6-trichloroρhenyl)-2,3-dihydro-l - benzofuran-2-yl]methanamine (1.1 g, 3.57 mmol) with diisopropylethylamine (0.69 g, 5.35 mmol) and benzyl chloroformate (0.0.82 g, 4.28 mmol) generally according to the procedure described for Intermediate 12 provided 1.6 g (99%) of (±)-benzyl methyl{[7- (2,4,6-trichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl }carbamate as a colorless oil.

Intermediate 221: (+)-benzyl {[7-(2,4,6-trichlorophenyl)-2,3-dihydro-l-benzofuran- 2-y 1] methyl} carbamate

Fraction 1 obtained as a colorless oil from the chiral HPLC separation of (±)- benzyl { [7-(2,4,6-trichlorophenyl)-2,3-dihydro- 1 -benzofuran-2-yl] methyl} carbamate. M _D ⁼ +7.8 (c 10.0 in methanol).

Intermediate 222: (-)-benzyl {[7-(2,4,6-trichlorophenyl)-2,3-dihydro-l-benzofuran- 2-yl] methyl} carbamate

Fraction 1 obtained as a colorless oil from the chiral HPLC separation of (±)- benzyl {[7-(2,4,6-trichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]me thyl}carbamate. [α] _D ⁵ = -6.2 (c 10.0 in methanol).

Intermediate 223: (±)-[7-bromo-5-(trifluoromethyl)-2,3-dihydro-l-benzofuran-2 - yl]methyl 4-methylbenzenesulfonate

Treatment of (±)-[7-bromo-5-(trifluoromethyl)-2,3-dihydro-l-benzofuran-2 - yljmethanol (3.59 g, 12.1 mmol) withj>-toluenesulfonyl chloride (3.6 g, 18.2 mmol) generally according to described for Intermediate 10 provided 3.82 g (70%) (±)-[7- bromo-5-(trifluoromethyl)-2,3-dihydro- 1 -benzofuran-2-yl]methyl 4- methylbenzenesulfonate. mp 95-97 °C.

Intermediate 224: (-)- [7-(2-methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl 4- methylbenzenesulfonate

Treatment of (-)-[7-bromo-2,3-dihydro-l-benzofuran-2-yl]methyl A- methylbenzenesulfonate (2.0 g, 5.22 mmol) with 2-methylphenylboronic acid (1.06 g, 7.83 mmol) generally according to described for Intermediate 37 provided 1.71 g (83%) (-)- [7-(2-methylphenyl)-2 _J 3-dihydro-l-benzofuran-2-yl]methyl A- methylbenzenesulfonate. [α]p = -44.6 (c 10.0 in methanol).

Intermediate 225: (S)-l-Benzyloxy-3-(5-fluoro-2-methoxy-phenyl)propan-2-ol To a solution of 4-fluoro-2-bromanisole (12.6 ml, 0.1 mol) in anhydrous tetrahydrofuran at -78 °C was added n-butyllithium (39 ml, 2.5 M in hexane) and the resulting mixture was allowed to stir at -78° C for 3 h. Copper(I) bromide- dimethylsulfide (10.0 g, 0.05 mol) was then added at -78 °C and the reaction mixture was allowed to warm to -40 °C over 2 h. Benzyl (S)-(+)-glycidyl ether (3.71 ml, 0.025 mol) was added at -60°C followed by boron trifluoride diethyl etherate (0.15 ml, 1.2 mmol) and the reaction mixture was allowed to warm to room temperature over 12 h. The solvent was removed in vacuo and purification by flash column chromatography (silica, ethyl acetate :hexanes 3:7) afforded 5.0 g (70%) of (jS)-l-benzyloxy-3-(5-fluoro-2- methoxy-phenyl)propan-2-ol as a colorless oil. HRMS ESI m/e 308.1666 [M+NH4] ⁺ , Calc'd m/e 308.1662 [M+NH4] ⁺ ; [α]" = +8.1 (c 0.89% in methanol).

Intermediate 226: (S)-l-Benzyloxy-3-(5-chloro-2-methoxy-phenyI)propan-2-ol

Treatment of 4-chloro-2-bromanisole (21.5 g, 0.1 mol) generally according to the procedure described for Intermediate 225 provided 5.1 g (67%) of (5)-l-benzyloxy-3-(5- chloro-2-methoxy-phenyl)propan-2-ol as a colorless oil. HRMS ESI m/e 307.1096 [M+H] ⁺ , Calc'd 307.1101; [<X] _D = +6.6 (c 1% in methanol).

Intermediate 227: (S)-l-BenzyIoxy-3-(2-methoxy-5-methyl-phenyl)propan-2-oI

Treatment of 2-bromo-4-methylanisole (14.05 ml, 0.1 mol) generally according to the procedure described for Intermediate 225 afforded 6.74 g (96%) of (<S)-l-benzyloxy- 3-(2-methoxy-5-methyl-phenyl)propan-2-ol as a colorless oil. HRMS EI m/e 286.1565

(M) ⁺ , Calc'd. 286.1569; [α]" = +15.67 (c 9.57 in methanol).

Intermediate 228: (S)-I -Benzyloxy-3-(2-methoxy-phenyl)propan-2-ol

Treatment of 2-bromoanisole (12.1 ml, 0.1 mol) generally according to the procedure described for Intermediate 225 gave 5.4 g (82%) of (S)-l-benzyloxy-3-(2- methoxy-phenyl)propan-2-ol as a colorless oil. HRMS EI m/e 272.1413 (M) ⁺ , CaIc 'd. 272.1412. [<X] _D = +18.07 (c 7.86 in methanol).

Intermediate 229: (S)-I -Benzyloxy~3-(2', 6'-dichlor-5-fluoro-2-methoxybiphenyl-3- yl)propan-2-ol To a solution of 3-bromo-2',6'-dichloro-5-fluoro-2-methoxy-biphenyl (2.2 g, 6.3 mmol) in anhydrous tetrahydrofuran at 0 ⁰ C was added isopropylmagnesium chloride (3.45 ml, 2.0 M in hexane) and the resulting mixture was allowed to stir at 0 ⁰ C for 4 h. The reaction mixture was cooled to -30 °C and copper(I) cyanide (0.28 g, 3.1 mmol) in tetrahydrofuran was added and the reaction mixture was allowed to stir at -30 °C for 1 h. Benzyl (S)-(+)-glycidyl ether (0.48 ml, 3.1 mmol) was then added at -30 °C and the reaction mixture was allowed to warm to room temperature for 12 h. The solvent was removed in vacuo and purification by flash column chromatography (silica, ethyl acetate :hexanes 3:7) provided 1.28 g (94%) of (S)-I -benzyloxy-3-(2', 6'-dichlor-5-fluoro- 2-methoxybiphenyl-3-yl)propan-2-ol as a colorless oil. HRMS ESI m/e 435.0946 [M - H] ^" , Calc'd 435.0930; [α]j-? = +2.8 (c 8.14 in dimethylsulfoxide).

Intermediate 230: (lS)-2-bromo-l-(5-fluoro-2-hydroxybenzyI)ethyl acetate

A solution of (iS>l-benzyloxy-3-(5-fluoro-2-memoxy-phenyl)propan-2-ol (5.17 g, 17.8 mmol) in hydrogen bromide (40 ml, 30 wt.% in acetic acid) was heated to 70 °C and allowed to stir for 12 h. The solvent was removed in vacuo and the residue was dissolved in dichloromethane and washed with ammonium hydroxide. The solvent was removed in vacuo and purification by flash column chromatography (silica, ethyl acetate :hexanes 3:7) afforded 3.60 g (70%) of (lS)-2-bromo-l-(5-fluoro-2~hydroxybenzyl)ethyl acetate as a light brown oil. Elemental Analysis for: CnH ₁₂ BrFO ₃ Theory: C, 45.38 H, 4.15 Found: C, 45.24 H, 4.09.

Intermediate 231: (lS)-2-bromo-l-(5-chloro-2-hydroxybenzyl)ethyl acetate

Treatment of (5)-l-benzyloxy-3-(5-chloro-2-methoxy-phenyl)propan-2-ol (5.4 g, 17.6 mmol) generally according to the procedure described for Intermediate 230 gave 3.8 g (70%) of (15)-2-bromo-l-(5-chloro-2-hydroxybenzyi)ethyl acetate as a light brown oil. HRMS EI m/e 305.9647 (M) ⁺ .

Intermediate 232: (lS)-2-bromo-l-(2-hydroxy-5-methylbenzyl)ethyl acetate

Treatment of (5)-l-benzyloxy-3-(2-methoxy-5-methyl-phenyl)propan-2-ol (6.7 g, 23.3mmol) generally according to the procedure described for Intermediate 230 provided 6.24g (93%) of (15)-2-bromo-l -(2-hydroxy-5-methylbenzyl)ethyl acetate as a yellow oil. MS EI m/e 286 (M) ⁺ ; [αβ ⁵ = -2.41 (c 8.29 in methanol).

Intermediate 233: (lS)-2-bromo-l-(2-hydroxybenzyl)ethyl acetate

Treatment of (,S)-l-benzyloxy-3-(2-methoxy-phenyl)propan-2-ol (5.40 g, 19.8 mmol) generally according to the procedure described for Intermediate 230 provided 3.42 g (63%) of (15)-2-bromo-l-(2-hydroxybenzyl)ethyl acetate as a yellow oil. [α]p ⁵ = -12.2 (c 1% in methanol). Elemental Analysis for: C ₁₆ Hi ₅ BrO ₃ Theory: C, 48.37 H, 4.80 Found: C, 48.48 H, 4.78.

Intermediate 234: 3-[(2S)-2-(acetyloxy)-3-bromopropyl]~2',6'-dichloro-5- fluorobiphenyl-2-yl acetate

Treatment of (5)-l-benzyloxy-3-(2' ₅ 6'-dichlor-5-fluoro-2-methoxybiphenyl-3- yl)propan-2-ol (1.28 g, 2.9 mmol) generally according to the procedure described for Intermediate 230 provided 1.12 g (80%) of 3-[(2S)-2-(acetyloxy)-3-bromopropyl]-2',6'- dichloro-5-fluorobiphenyl-2-yl acetate as a light yellow oil. HRMS ESI m/e 476.9686 [M+H] ⁺ , Calc'd. 476.9671; [α]^ ⁵ = +13.2 (c 1% in methanol).

Intermediate 235: (S)-2-(3-Bromo-2-hydroxy-propyl)-4-fluoro-phenol

To a solution of (15)-2-bromo-l-(5-fluoro-2-hydroxybenzyl)ethyl acetate (3.57 g, 12.2 mmol) in methanol was added hydrogen chloride (1.0 M in diethylether, 49 ml) and the reaction mixture was allowed to stir at room temperature for 12 h. The solvent was removed in vacuo and purification by flash column chromatography (silica, ethyl

acetate:hexanes 3:7) afforded 2.95 g (97%) of (£)-2-(3-bromo-2-hydroxy~propyi)-4- fluoro-phenol as a colorless oil. HRMS ESI m/e 246.9761 [M-H] ⁺ ; Calc'd 246.9755. [CC] _D = +8.2° (c 0.71% in methanol).

Intermediate 236: (S)-2-(3-Bromo-2-hydroxy-propyl)-4-chIoro-phenol

Treatment of (liS)-2-bromo-l-(5-chloro-2-hydroxybenzyl)ethyl acetate (2.47 g, 3.2 mmol) generally according to the procedure described for Intermediate 235 gave 1.68 g (79%) of (S)-2-(3-bromo-2-hydroxy-propyl)-4-chloro-phenol as a yellow oil. [α]^ ⁵ = +9.8° (c 1% in methanol), HRMS EI m/e 263.956 (M) ⁺ .

Intermediate 237: (S)-2-(3-Bromo-2-hydroxy-propyl)-4-methyI-phenol

Treatment of (15)-2-bromo-l-(2-hydroxy-5-methylbenzyl)ethyl acetate (6.24 g, 22 mmol) generally according to the procedure described for Intermediate 235 afforded 5.0 g (94%) of (5)-2-(3-bromo-2-hydroxy-propyl)-4-methyl-phenol as a colorless oil. [α]^ ⁵ = +13.8 (c 1% in methanol), HRMS ESI m/e 243.0020 [M-H] ^" , Calc'd. 243.0021.

Intermediate 238: (S)-2-(3-Bromo-2-hydroxy-propyl)-phenol

Treatment of (15)-2-bromo-l-(2-hydroxybenzyl)ethyl acetate (3.42 g, 12.5 mmol) generally according to the procedure described for Intermediate 235 provided 2.71 g (93%) of (S)-2-(3-bromo-2-hydroxy-proρyl)-phenol as a light yellow oil. MS ES m/e 229.0 [M-H] ^" ; [α] ² _D ⁵ = +16.46 (c 8.14 in methanol).

Intermediate 239: (S)-3-(3-Bromo-2-hydroxy-propyl)-2',6',-dichloro-5-fluoro- biphenyl-2-ol Treatment of 3-[(25)-2-(acetyloxy)-3-bromopropyl]-2',6 ^r -dichloro-5- fluorobiphenyl-2-yl acetate (1.6 g, 33.4 mmol) generally according to the procedure described for Intermediate 235 gave 1.48 g (99%) of (S)-3-(3-bromo-2-hydroxy-propyl)- 2',6',-dichloro-5-fluoro-biphenyl-2-ol as a light yellow oil. HRMS EI m/e 391.9391 (M) ⁺ , Calc'd. 391.9391; [αβ ⁵ = -4.76 (c 7.14 in methanol).

Intermediate 240 : (R)-2-Bromomethyl-5-fluoro-2,3-dihy dro-benzofuran

Treatment of (S)-2-(3-bromo-2-hydroxy-propyl)-4-fluoro-phenol (1.97 g, 8 mmol), triphenylphosphine (5.2 g, 20 mmol), and diethylazodicarboxylate (3.11 ml, 20 mmol) generally according to the procedure described for Intermediate 18 afforded 1.40 g (76%) of (i?)-2-bromomethyl-5-fluoro-2,3-dihydro-benzofuran as a colorless oil. HRMS ESI m/e 228.9661 [M-H] ^" . [α]^ ⁵ = -33.0 (c 1% in methanol).

Intermediate 241 : (i?)-2-Bromomethyl-5-methyl-2,3-dihydro~benzofuran

Treatment of (5)-2-(3-bromo-2-hydroxy-propyl)-4-methyl-phenol (5.0 g, 20 mmol) generally according to the procedure described for Intermediate 18 gave 3.04 g

(70%) of (i?)-2-bromomethyl-5-methyl-2,3-dihydro-benzofuran as a yellow oil. HRMS EI m/e 225.9998 (M) ⁺ ; [α]n = -41.13 (c 8.86 in methanol).

Intermediate 242: (J?)-2-Bromomethyl-2,3-dihydro-benzofuran Treatment of (£)-2-(3-bromo-2-hydroxy-propyl)-phenol (2.71 g, 12 mmol) generally according to the procedure described for Intermediate 18 provided 1.62g (65%) of (i?)-2-bromomethyl-2,3-dihydro-benzofuran as a yellow oil. [α]^ ⁵ = -37 (c 1% in methanol); HRMS EI m/e 211.9840 (M) ⁺ , Calc'd. 211.9837.

Intermediate 243: (i?)-2-Bromomethyl-7-(2',6'-dichloro-phenyl)-5-fluoro-2,3- dihydro-benzofuran

Treatment of (5)-3-(3-bromo-2-hydroxy-propyl)-2',6',-dichloro-5-fluoro- biphenyl-2-ol (1.48 g, 3.7 mmol) generally according to the procedure described for Intermediate 18 afforded 1.16 g (82%) of (i?)-2-bromomethyl-7-(2',6'-dichloro-phenyl)- 5-fluoro-2,3-dihydro-benzofuran as a colorless oil. HRMS EI m/e 373.9277 (M) ⁺ , Calc'd. 373.9277; [αβ ⁵ = -15.75 (c 8.0 in methanol).

Intermediate 244: (R)-7-Bromo-2-bromomethyl-5-fluoro-2,3-dihydrobenzofuran

To a solution of (i-)-2-bromomethyl-5-fluoro-2,3-dihydro-benzofuran (3.20 g, 14 mmol) in acetic acid was added bromine (2.2 ml, 42 mmol) and the reaction mixture was allowed to stir at room temperature for 12 h. The solvent was removed in vacuo and the residue dissolved in dichloromethane and washed with saturated aqueous sodium sulfite.

The solvent was removed in vacuo and purification by flash column chromatography (silica, ethyl acetate:hexanes 1 :19) afforded 3.16 g (74%) of as a light yellow oil. HRMS EI m/e 307.8846 (M) ⁺ , Calc'd. 307.8848. [af _O ⁵ = +24.8 (c 1% in methanol).

Intermediate 245: (l?)-2-Bromomethyl-5-fluoro-7-o-toIy-2,3-dihydrobenzofuran

Treatment of (i?)-7-bromo-2-bromomethyl-5-fluoro-2,3-dihydrobenzofuran (2.57 g, 8.2 mmol) and o-tolyboronic acid (3.4 g, 24 mmol) generally according to the procedure described for Intermediate 37 afforded 2.54 g (95%) of (i?)-2-Bromomethyl-5- fluoro-7-o-toly-2,3-dihydrobenzofuran as a colorless oil. HRMS EI m/e 320.0224 (M) ⁺ ; [<X]D = +35.00 (c 1% in methanol).

Intermediate 246: (l?)-2-Bromomethyl-7-(2-chloro-phenyl)-5-fluoro-2,3- dihydrobenzofuran

Treatment of (i?)-7-bromo-2-bromomethyl-5-fluoro-2,3-dihydrobenzofuran (0.5 g, 1.6 mmol) and 2-chlorobenzene boronic acid (0.76 g, 4.8 mmol) generally according to the procedure described for Intermediate 37 gave 0.55 g (99%) (i?)-2-bromomethyl-7-(2- chloro-phenyl)-5-fluoro-2,3-dihydrobenzofuran as a colorless oil. HRMS EI M ⁺ 339.9657; [α]^ ⁵ = +29.6 (c 8.14 in methanol).

Intermediate 247: (R)-2-Bromomethyl-7-(2-methyl-5-chloro -phenyl)-5-fluoro-2,3- dihydrobenzofuran

Treatment of (i?)-7-bromo-2-bromomethyl-5-fluoro-2,3-dihydrobenzofuran (0.40 g, 1.3 mmol) and 5-chloro-o-toluene boronic acid (0.88 g, 5.2 mmol) generally according to the procedure described for Intermediate 37 provided 0.41 g (90%) of (R)-2- bromomethyl-7-(2-methyl-5-chloro -phenyl)-5-fluoro-2,3-dihydrobenzofuran as a colorless oil. HRMS EI M ⁺ 353.9829; [<X]D = +47.38 (c 9.29 in methanol).

Intermediate 248: (λ)-2-Bromomethyl-7-(2-methyl-4-chloro -phenyl)-5-fluoro-2,3- dihydrobenzofuran Treatment of (i?)-7-bromo-2-bromomethyl-5-fluoro-2,3-dihydrobenzofuran (0.42 g, 1.3 mmol) and 4-chloro-o-toluene boronic acid (0.88 g, 5.2 mmol) generally according to the procedure described for Intermediate 37 provided 0.43 g (95%) of (R)-2-

bromomethyl-7-(2-methyl-4-chloro -phenyl)-5-fluoro-2,3-dihydrobenzofuran as a colorless oil. HRMS EI M ⁺ 353.9825, Calc'd. 353.9825; [<X] _D = +39.14 (c 7.0 in methanol).

Intermediate 249: (λ)-2-AzidomethyI-7-(4-chloro-2-methyl-phenyl)-5-fluoro-2,3 - dihydrobenzofuran

Treatment of (i?)-2-Bromomethyl-7-(4-chloro-2-methyl-phenyl)-5-fluoro-2,3 - dihydrobenzofuran (0.4 g, 1.1 mmol) generally according to the procedure described for Intermediate 98 gave 0.30 g (85%) of (i?)-2-azidomethyl-7-(4-chloro-2-methyl-phenyl)-5- fluoro-2,3-dihydrobenzofuran as a colorless oil. HRMS EI m/e 317.0719 (M) ⁺ , Calc'd. 317.0718; [αβ ⁵ = +16.76 (c 8.71 in methanol).

Intermediate 250: (l?)-2-AzidomethyI-7-(5-chloro-2-methyl-phenyl)-5-fluoro~2,3 - dihydrobenzofuran Treatment of 2-bromomethyl-7-(5-chloro-2-methyl-phenyl)-5-fluoro-2,3- dihydroben-zofuran (0.41 g, 1.2 mmol) generally according to the procedure described for Intermediate 98 gave 0.31 g (85%) of (i?)-2-azidomethyl-7-(5-chloro-2-methyl-phenyl)-5- fluoro-2,3-dihydrobenzofuran as a colorless oil. HRMS EI m/e 317.0734 (M) ⁺ , Calc'd. 317.0733; [α]^ ⁵ = +3.12 (c 7.71 in methanol).

Example 1: (±)-l-(4-phenyl-2,3-dihydro-l~benzofuran-2-yl)methanamine

Treatment of (±)-(4-phenyl-2,3 -dihydro- 1 -benzofuran-2-yl)methyl 4- methylbenzenesulfonate (1.36 g, 3.57 mmol) with sodium azide (0.929 g, 14.29 mmol) generally according to the procedure described for intermediate 98 afforded (±)-(4- phenyl-2,3-dihydro-l-benzofuran-2-yl)methyl azide. The azide was dissolved in ethanol (50 mL) and palladium on carbon (0.083 g, 10 wt.%) was added and the reaction mixture was shaken under an H2 atmosphere (50 psi) for 6 h. The reaction mixture was filtered

(celite) and the solvent removed in vacuo to provide a colorless oil. The oil was re- dissolved in isopropanol (3 mL) and hydrogen chloride (1.0 N in diethyl ether, 10.0 mL) was added. The resulting precipitate was filtered, washed (diethyl ether), and dried to afford 0.700 g (94%) of (±)-l-(4-ρhenyl-2,3-dihydro-l-benzofuran-2-yl)methanamine as

a white solid, hydrochloride salt, mp 229-230 ⁰ C; Anal, calcd. for C ₁₅ H ₁₅ NOHCl: C, 68.83; H, 6.16; N ₅ 5.35. Found: C, 66.11; H ₅ 6.25; N, 5.02.

Example 2: (+)-l-(4-phenyl-2,3-dihydro-l-benzofuran-2-yl)methanamine Fraction 1 (0.206 g) obtained from the chiral HPLC separation of (±)-benzyl (4- phenyl-2,3-dihydro-l-benzofuran-2-yl)methylcarbamate (Chiralcel OD, ethanol:water 15:85) was treated with hydrogen bromide (3 mL, 30 wt.% in acetic acid) and the reaction mixture was allowed to stir at room temperature for 30 min. Diethyl ether (20 mL) was added to the reaction mixture and the resulting precipitate was filtered, washed with diethyl ether, and dried to afford 0.082g (46%) of (+)-l-(4-phenyl-2,3-dihydro-l- benzofuran-2-yl)methanamine as a tan solid, hydrobromide salt. [α] _D = +86.92 (c 10.0 in methanol); mp 225-226 °C; Anal, calcd. for C ₁₅ H ₁₅ NOHBr: C, 58.84; H, 5.27; N, 4.57. Found: C, 57.02; H, 4.96; N ₅ 4.3.

Example 3: (-)-l-(4-phenyl-2,3-dihydro-l-benzofuran-2-yl)methanamine

Treatment of 0.197 g of fraction 2 obtained from the chiral HPLC separation of (±)-benzyl (4-phenyl-2,3-dihydro-l-benzofuran-2-yl)methylcarbamate, (Chiralcel OD ₅ ethanol:water 15:85) with hydrogen bromide (3 mL, 30 wt.% in acetic acid) generally according to the procedure described for Example 2 gave 0.091 g (54%) of (-)-l-(4- phenyl-2,3-dihydro-l-benzofuran-2-yl)methanamine as a tan solid, hydrobromide salt. [α]o = -84.76 (c 10.0 in methanol); mp 227-228 °C; Anal, calcd. for C ₁₅ H ₁₅ NOHBr: C, 58.84; H, 5.27; N ₅ 4.57. Found: C, 57.19; H ₅ 5.19; N ₅ 4.18.

Example 4: (±)-l-[4-(2-methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]met hanamine Treatment of (±)-[4-(2-methylphenyl)-2 ₅ 3-dihydro-l-benzofuran-2-yl]methyl A- methylbenzenesulfonate (1.31 g, 3.32 mmol) with sodium azide (0.863 g, 13.28 mmol) generally according to the procedure described for Intermediate 98 afforded (±)-2- (azidomethyl)-4-(2-methylphenyl)-2,3-dihydro-l-benzofuran. Treatment of the azide with palladium on carbon (0.082 g, 10 wt.%) generally according to the procedure described for Example 1 provided 0.689 g (85%) of (±)-l-[4-(2-methylphenyl)-2,3-dihydro-l- benzofuran-2-yl]methanamine as a white solid, hydrochloride salt, mp 231-234 °C; Anal.

calcd. for CI ₆ HI ₇ NOHCI-O^ H2O: C, 68.79; H, 6.64; N, 5.01. Found: C, 68.49; H, 6.50; N ₅ 4.87.

Example 5: (+)-l-[4-(2-methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]meth anamine Treatment of 0.236 g of fraction 1 obtained from the chiral HPLC separation of

(±)-benzyl [4-(2-methylphenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methylcarbamate (Chiralcel OD, methanol) with hydrogen bromide (3 mL, 30 wt.% in acetic acid) generally according to the procedure described for Example 2 gave 0.167 g (83%) of (+)- l-[4-(2-methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methanam ine as a white solid, hydrobromide salt, [α]" = +89.44 (c 10.0 in methanol); mp 232-233 °C; Anal, calcd. for Ci ₆ Hi ₇ NOHBr: C, 60.01; H, 5.67; N, 4.37. Found: C, 59.28; H, 5.36; N ₅ 3.8.

Example 6: (-)-l-[4-(2-methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]meth anamine

Treatment of 0.229 g of fraction 2 obtained from the chiral HPLC separation of(±)-benzyl [4-(2-methylphenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methylcarbamate (Chiralcel OD, methanol) with hydrogen bromide (3 mL, 30 wt.% in acetic acid) according the procedure described for Example 2 afforded 0.190 g, (97%) of (-)-l-[4-(2- methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine as a white solid, hydrobromide salt. [<X] _D = -83.96 (c 10.0 in methanol); mp 231-233 °C; Anal, calcd. for Ci ₆ Hi ₇ NOHBr: C, 60.01; H, 5.67; N, 4.37. Found: C, 59.37; H, 5.64; N, 3.98.

Example 7: (±)-l-(7-methoxy-2,3-dihydro-l-benzofuran-2-yI)methanamine

Treatment of (±)-(7-methoxy-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate (1.00 g, 2.99 mmol) with sodium azide (0.78 g, 11.96 mmol) generally according to the procedure described for Intermediate 98 provided (±)-2- (azidomethyl)-7-methoxy-2,3-dihydro-l-benzofuran. Treatment of the azide with palladium on carbon (0.06 g, 10 wt.%) generally according to the procedure described for Example 1 afforded 0.465 g (54%) (±)-l-(7-methoxy-2,3-dihydro-l-benzofuran-2- yl)methanamine as a white solid, hydrochloride salt, mp 168-171 °C; Anal, calcd. for C10H13NO2HCI: C, 55.69; H ₅ 6.54; N ₅ 6.49. Found: C ₅ 55.68; H ₅ 6.52; N ₅ 6.5.

Example 8: (±)-(7-cyclopentyI-2,3-dihydro-l-benzofuran-2-yI)methylamin e

Treatment of (±)-(7-cyclopentyl-2,3-dihydro-l-benzofuran-2-yl)methanol (4.08 g, 18.7 mmol) with/>-toluenesulfonyl chloride (3.92 g, 21.9 mmol) in anhydrous pyridine (76 mL) generally according to the procedure described for Intermediate 10 gave (±)-(7- cyclopentyl-2,3-dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate as a tan oil. Treatment of the tosylate with sodium azide (4.39 g, 67.57 mmol) generally according to the procedure described for Intermediate 98 afforded 4.1 g of (±)-2-(azidomethyl)-7- cyclopentyl-2,3-dihydro-l-benzofuran as a yellow oil. Treatment of the azide with palladium on carbon (0.41 g, 10 wt.%) generally according to the procedure described for Example 1 afforded 2.5 g (58%) of (±)-(7-cyclopentyl-2,3-dihydro-l-benzofuran-2- yl)methylamine as a white solid, hydrochloride salt, mp 174 °C; Anal, calcd. for C ₁₄ H ₁₉ ON ₂ HCl: C, 66.26; H, 7.94; N, 5.52. Found C, 66.13; H, 7.71; N ₃ 5.5.

Example 9: (-)-(7-cyclopentyl-2,3-dihydro-l-benzofuran-2-yl)methylamine Treatment of 0.833 g of fraction 1 obtained from the chiral HPLC separation of(±)-(7-cyclopentyl-2,3-dihydro- 1 -benzofuran-2-yl)methylcarbamate (Chiralcel OJ, ethanol:hexane 1:1) with hydrogen bromide (12.0 mL, 30 wt.% in acetic acid) generally according to the procedure described for Example 2 gave 0.541 g (76%) of (-)-(7- cyclopentyl-2,3-dihydro-l-benzofuran-2-yl)methylamine as a tan solid, hydrobromide salt. [CC]D = -13.4 (c 10.0 in methanol); mp 208-211 ⁰ C; Anal, calcd. for C ₁₄ H ₁₉ NOHBr:

C, 56.39; H, 6.76; N, 4.7. Found: C, 55.83; H, 6.54; N, 4.41.

Example 10: (+)-(7-cyclopentyl-2,3-dihydro-l-benzofuran-2-yl)methylamine

Treatment of 0.760 g of fraction 2 obtained from the chiral HPLC separation of(±)-(7-cyclopentyl-2,3-dihydro-l-benzofuran-2-yl)methylca rbamate (Chiralcel OJ, ethanol:hexane 1 :1) with hydrogen bromide (11.0 mL, 30 wt.% in acetic acid) generally according to the procedure described for Example 2 afforded 0.468 g (72%) of (+)-(7- cyclopentyl-2,3-dihydro-l-benzofuran-2-yl)methylamine as a tan solid, hydrobromide salt, [αj _ϋ ⁵ = +11.5 (c 10.0 in methanol); Anal, calcd. for C ₁₄ H ₁₉ NOHBr: C, 56.39; H ₅ 6.76; N, 4.7. Found: C, 56.03; H, 6.71; N, 4.63.

Example 11 : (±)-(5-chloro-7-cyclohexyl-2,3-dihydro-l-benzofuran-2-yl)me thylamme

Treatment of (±)-(5-chloro-7-cyclohexyl-2,3-dihydro-l-benzofuran-2-yl)me thanol (4.5 g, 0.017 mol) with/Moluenesulfonyl chloride (4.8 g, 0.025 mol), diisopropylethylamine (4.36 g, 0.034 mol), and 4-(dimethylamino)pyridine (0.12 g, 0.98 mmol) generally according to the procedure described for Intermediate 45 gave (±)-(5- chloro-7-cyclohexyl-2,3-dihydro- 1 -benzofuran-2-yl)methyl 4-methylbenzenesulfonate as a colorless oil. Treatment of the tosylate with sodium azide (4.03 g, 61.99 mmol) generally according to the procedure described for Intermediate 98 provided 3.45 g of (±)-2-(azidomethyl)-5-chloro-7-cyclohexyl-2,3-dihydro-l -benzofuran. Treatment of the azide with sulfided platinum on carbon (0.75 g, 5 wt.%) generally according to the procedure described for Example 1 afforded 2.70 g (60%) of (±)-(5-chloro-7-cyclohexyl- 2,3-dihydro-l-benzofuran-2-yl)methylamine as a white solid, hydrochloride salt, mp 210- 213 °C; Anal, calcd for C ₁₅ H ₂ OClNOHCl: C, 59.61; H, 7.00; N ₅ 4.63. Found: C, 57.29;

H, 7.14; N, 4.78.

Example 12: (±)-iV-[(5-chloro-7-cyclohexyl-2,3-dihydro-l-benzofuran-2-y l)methyl]- N-methylamin e

To a suspension of lithium aluminum hydride (0.114 g, 3.0 mmol) in tetrahydrofuran (30 mL) was added (±)-methyl (5-chloro-7-cyclohexyl-2,3-dihydro-l- benzofuran-2-yl)methylcarbamate (0.65 g, 2.0 mmol) and the reaction mixture was allowed to stir at room temperature for 30 h. The reaction mixture was quenched with saturated ammonium chloride (50 mL), diluted with tetrahydrofuran (70 mL), and the aqueous layer was extracted with tetrahydrofuran (2 x 50 mL). The combined organic layers were washed with saturated aqueous sodium bicarbonate (100 mL) and saturated aqueous sodium chloride (100 mL), were dried (sodium sulfate), and the solvent was removed in vacuo to provide a crude oil. Purification by flash column chromatography (silica, dichloromethane: methanol 97:3) gave a light brown oil. The oil was re-dissolved in tetrahydrofuran (50 mL) and aqueous hydrogen chloride (1 N, 3 mL) was added. The resulting precipitate was filtered and washed with diethyl ether to provide 0.28 g (44%) of (±)-iV- [(5-chloro-7-cyclohexyl-2,3 -dihydro- 1 -benzofuran-2-yl)methyl] -N-methylamine as a white solid, hydrochloride salt, mp 125-128 ⁰ C; Anal, calcd. for CIgH ₂₂ ClNOHCl: C ₅

60.76; H ₅ 7.33; N ₅ 4.43. Found: C ₅ 60.92; H, 7.46; N ₅ 4.09.

Example 13: (±)-(7-te^-butyl-5-methoxy-2,3-dihydro-l-benzofuran-2- yl)methylamine

Treatment of 2-tert-butyl-4-methoxyphenol and 3-tert-butyl-4-methoxyphenol (18.25 g, 0.101 mol) with potassium carbonate (55.28 g, 0.400 mol) and allyl bromide (14.69 g, 0.121 mol) followed by treatment of the resultant allyl ether in refluxing mesitylene generally according to the procedure described for Intermediate 8 provided 2- allyl-6-ført-butyl-4-methoxyphenol and 2-allyl-5-tert-butyl-4-methoxyphenol. Treatment of the phenol with 3-chloroperoxybenzoic acid (49.58 g, 0.287 mol, 77%) and potassium carbonate (33.0 g, 0.238 mol) generally according to the procedure described for Intermediate 9 gave 3.23 g (14%) of (±)-(7-tert-butyl-5-methoxy-2,3-dihydro-l- benzofuran-2-yl)methanol as a white solid. Treatment of the benzofuran with /?- toluenesulfonyl chloride (2.86 g, 0.015 mol) generally according to the procedure described for Intermediate 10 afforded (±)-(7-tert-butyl-5-methoxy-2,3-dihydro-l- benzofuran-2-yl)methyl 4-methylbenzenesulfonate. Treatment of the tosylate with sodium azide (1.46 g, 22.5 mmol) generally according to the procedure described for Intermediate 98 gave (±)-2-(azidomethyl)-7-ført~butyl-5-methoxy-2,3 -dihydro- 1 -benzofuran. Treatment of the azide with palladium on carbon (0.14 g, 10 wt.%) generally according to the procedure described for Example 1 afforded 1.5 g (40%) of (±)-(7-tert-butyl-5- methoxy-2,3 -dihydro- l-benzofuran-2-yl)methylamine) as a white solid, hydrochloride salt, mp 174-176 °C; Anal calcd. for CHH ₂ IO ₂ NHCI: C, 61.87; H, 8.16; N, 5.15. Found

C, 61.67; H, 8.37; N, 4.93.

Example 14: (±)-[7-chloro-4-(trifluoromethyl)-2,3-dihydro-l-benzofuran- 2- yljmethanamine

Treatment of (±)- [7-chloro-4-(trifluoromethyl)-2,3 -dihydro- 1 -benzofuran-2- yl]methyl 4-methylbenzenesulfonate (1.0 g, 2.46 mmol) with sodium azide (0.64 g, 9.83 mmol) generally according to the procedure described for Intermediate 98 provided (±)-2- (azidomethyl)-7-chloro-4-(trifluoromethyl)-2,3 -dihydro- 1 -benzofuran. Treatment of the azide with palladium on carbon (0.060 g, 10 wt.%) generally according to the procedure described for Example 1 afforded 0.350 g (64%) of (±)-l-[7-chloro-4-(trifiuoromethyl)- 2,3-dihydro-l-benzofuran-2-yl]methanamine as a white solid, hydrochloride salt, mp

>250 °C; Anal, calcd. for C ₁₀ H ₉ F ₃ ClNOHCl: C, 41.69; H, 3.5; N ₅ 4.86. Found: C, 41.78; H, 3.43; N ₅ 4.77.

Example 15: (±)-l-(7-benzyl-2,3-dihydro-l-benzofuran-2-yl)methanamine Treatment of (±)-(7-benzyl-2,3-dihydro- 1 -benzofuran-2-yl)methyl 4- methylbenzenesulfonate (6.53 g, 16.6 mmol) with sodium azide (4.30 g, 66.2 mmol) generally according to the procedure described for Intermediate 98 afforded (±)-(7- benzyl-2,3-dihydro-l-benzofuran-2-yl)methyl azide. Treatment of the azide with palladium on carbon (0.40 g, 10 wt.%) generally according to the procedure described for Example 1 gave 3.62 g (79%) of (±)-l-(7-benzyl-2,3-dihydro-l-benzofuran-2- yl)methanamine as a white solid, hydrochloride salt, mp 107-111 °C (dec); Anal, calcd. for CI ₆ HI ₇ NOHCI: C, 69.69; H, 6.58; N, 5.08. Found: C, 68.56; H, 6.66; N, 4.92.

Example 16: (+)-l-(7-benzyl-2,3-dihydro-l-benzofuran-2-yl)methanamine Treatment of 1.528 g of fraction 1 obtained from the chiral HPLC separation of(±)-benzyl (7-benzyl-2,3-dihydro-l-benzofuran-2-yl)methylcarbamate (Chiralcel OD, methanol) with palladium on carbon (0.15 g, 10 wt.%) generally according to the procedure described for Example 1 gave 0.781 g (69%) of (+)-l-(7-benzyl-2,3-dihydro-l- benzofuran-2-yl)methanamine as a white solid, hydrochloride salt. [α]β ⁵ = +15.1 (c 10.0 in methanol); mp 128-131 °C; Anal, calcd. for C ₁₆ H ₁₇ NOHCl: C, 69.69; H, 6.58; N, 5.08. Found: C, 69.14; H, 6.51; N, 5.03.

Example 17: (-)-l-(7-benzyl-2,3-dihydro-l-benzofuran-2-yl)methanamine

Treatment of 0.792 g of fraction 2 obtained from the chiral HPLC separation of(±)-benzyl (7-benzyl-2,3-dihydro-l-benzofuran-2-yl)methylcarbamate (Chiralcel OD, methanol) with palladium on carbon (0.08 g, 10 wt.%) generally according to the procedure described for Example 1 gave 0.415 g (71%) of (-)-l-(7-benzyl-2,3-dihydro-l- benzofuran-2-yl)methanamine as a white solid, hydrochloride salt, [α]" = -15.3 (c 10.0 in methanol); mp 128-131 ⁰ C; Anal, calcd. for C ₁₆ H ₁₇ NOHCl: C, 69.69; H, 6.58; N, 5.08. Found: C, 69.29; H, 6.59; N, 5.06.

Example 18: (±)-(7-isopropyl-2,3-dihydro-l-benzofuran-2-yl)methylamine

Treatment of (±)-(7-isopropyl-2,3-dihydro-l-benzofman-2-yl)methyl 4- methylbenzenesulfonate (5.15 g, 14.9 mmol) with sodium azide (3.87 g, 59.5 mmol) generally according to the procedure described for Intermediate 98 afforded (±)-(7- isopropyl-2,3-dihydro- 1 -benzofuran-2-yl)methyl azide. Treatment of the azide with palladium on carbon (0.30 g, 10 wt.%) generally according to the procedure described for Example 1 gave 2.35 g (69%) of (±)-(7-isopropyl-2,3-dihydro-l-benzofuran-2- yl)methylamine as a white solid, hydrochloride salt, mp 160-164 °C (dec); Anal, calcd. for C ₁₂ Hi ₇ NOHCl: C, 63.29; H, 7.97; N, 6.15. Found: C, 63.33; H, 7.98; N, 6.15.

Example 19: (-)-(7-isopropyI-2,3-dihydro-l-benzofuran-2-yI)methyIamine

Treatment of 0.891 g of fraction 1 obtained from the chiral HPLC separation of(±)-benzyl (7-isopropyl-2,3-dihydro-l-benzofuran-2-yl)methylcarbamate (Chiralcel OJ, ethanol) with palladium on carbon (0.09 g, 10 wt.%) generally according to the procedure described for Example 1 gave 0.475 g (76%) of (-)-(7-isopropyl-2,3-dihydro-l- benzofuran-2-yl)methylamine as a white solid, hydrochloride salt, [α]^ ⁵ = -34.09 (c 10.0 in methanol); mp 176-178 °C; Anal, calcd. for C ₁₂ Hi ₇ NOHCl: C, 63.29; H, 7.97; N, 6.15. Found: C, 63.32; H, 8.07; N, 6.14.

Example 20: (+)-(7-isopropyl-2,3-dihydro-l-benzofuran-2-yI)methyIamine

Treatment of 0.11 β g of fraction 2 obtained from the chiral HPLC separation of(±)-benzyl (7-isopropyl-2,3-dihydro-l-benzofuran-2-yl)methylcarbamate (Chiralcel OJ, ethanol) with palladium on carbon (0.09 g, 10 wt.%) generally according to the procedure described for Example 1 gave 0.445 g (82%) of (+)-(7-isopropyl-2,3-dihydro-l- benzofuran-2-yl)methylamine as a white solid, hydrochloride salt, [α]" = +32.18 (c 10.0 in methanol); mp 176-178 ⁰ C; Anal, calcd. for CI ₂ HI ₇ NOHCI: C, 63.29; H, 7.97; N, 6.15. Found: C, 63.86; H, 8.06; N, 6.00.

Example 21: (±)-l-(5-chIoro-7-isopropyl-4-methyl-2,3-dihydro-l-benzofur an-2- yl)methanamme

Treatment of (±)-(5-chloro-7-isopropyl-4-methyl-2,3-dihydro- 1 -benzofuran-2- yl)methyl 4-methylbenzenesulfonate (6.64 g, 16.8 mmol) with sodium azide (3.28 g, 50.4

mmol) generally according to the procedure described for Intermediate 98 afforded (±)-2- (azidomethyl)-5-chloro-7-isopropyl-4-methyl-2,3-dihydro-l-be nzofuran. To a solution of (±)-2-(azidomethyl)-5-chloro-7-isopropyl-4-methyl-2,3-dihyd ro-l-benzofuran (4.44 g, 16.71 mmol) in tetrahydrofuran (100 mL) was added triphenylphoshine (5.25 g, 20.05 mmol) followed by water (10 mL) and the reaction mixture was allowed to stir at room temperature for 12 h. The solvent was removed in vacuo to provide a crude solid. Purification by flash column chromatography (silica, 10% ammonium hydroxide in methanol: ethyl acetate 1 :9) provided a colorless oil. The oil was re-dissolved in isopropanol (5 mL) and hydrogen chloride (20.0 mL, 1.0 N in diethyl ether) was added. The resulting precipitate was filtered, washed (diethyl ether), and dried to afford 4.08 g (88%) of (±)-l-(5-chloro-7-isopropyl-4-methyl-2,3-dihydro-l-benzofur an-2- yl)methanamine as a white solid, hydrochloride salt, mp >225 °C (dec); Anal, calcd. for C ₁₃ HI ₈ CINOHCI: C ₃ 56.53; H, 6.93; N, 5.07. Found: C, 56.56; H, 6.91; N, 4.94.

Example 22: (-)-l-(5-chIoro-7-isopropyl-4-methyl-2,3-dihydro-l-benzofura n-2- yl)methanamine

To 1.61 g of fraction 1 obtained from the chiral HPLC separation of(±)-benzyl (5- chloro-7-isopropyl-4-methyl-2,3-dihydro- 1 -benzofuran-2-yl)methylcarbamate (Chiralpak AD, ethanol) was added hydrogen bromide (20 mL, 30 wt.% in acetic acid) and the resulting solution was allowed to stir at room temperature for 3 h. The reaction mixture was diluted with water and neutralized with 2.0 N aqueous sodium hydroxide. The reaction mixture was extracted with ethyl acetate (2 x 100 mL), the combined organic layers were washed with water (100 mL) and saturated aqueous sodium chloride (100 mL), were dried (magensium sulfate), and the solvent was removed in vacuo to provide a crude oil. Purification by flash column chromatography (silica, 10% aqueous ammonium hydroxide in methanol: ethyl acetate 1:9) provided a colorless oil. The oil was re- dissolved in isopropanol (2 mL) and hydrogen chloride (6 mL, 1.0 M in diethyl ether) was added. The rsulting precipitate was filtered, washed (diethyl ether), and dried to give 0.52 g (44%) of (-)-l-(5-chloro-7-isopropyl-4-methyl-2,3-dihydro-l-benzofura n-2- yl)methanamine as a white solid, hydrochloride salt, [α]^ ⁵ = -53.20 (c 10.0 in methanol); mp >225 ⁰ C; Anal, calcd. for C ₁₃ HI ₈ CINOHCI: C, 56.53; H, 6.93; N, 5.07. Found: C, 56.61; H, 7.06; N, 5.07.

Example 23: (+)-l-(5-chloro-7-isopropyI-4-methyl-2,3-dihydro-l-benzofura n-2- yl)methanamine

Treatment of 1.49 g of fraction 2 obtained from the chiral HPLC separation of(±)- benzyl (5-chloro-7-isopropyl-4-methyl-2,3-dihydro-l-benzofuran-2-yl )methylcarbamate (Chiralpak AD, ethanol) with hydrogen bromide (20 mL, 30 wt.% in acetic acid) generally according to the procedure described for Example 22 afforded 0.456 g (42%) of (+)- 1 -(5-chloro-7-isopropyl-4-methyl-2,3 -dihydro- 1 -benzofuran-2-yl)methanamine as a white solid, hydrochloride salt. [CC] _D = +51.30 (c 10.0 in methanol); mp >225 °C; Anal. calcd. for CI ₃ HI ₈ CINOHCI: C, 56.53; H, 6.93; N, 5.07. Found: C, 56.52; H, 7.06; N, 5.03.

Example 24: (±)-l-(7-ter/-butyl-2,3-dihydro-l-benzofuran-2-yI)methanami ne

Treatment of (±)-(7-fert-butyl-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate (12.43 g, 0.035 mol) with sodium azide (6.73 g, 0.103 mol) generally according to the procedure described for Intermediate 98 afforded (±)-2- (azidomethyl)-7-tert-butyl-2,3 -dihydro- 1-benzofuran. Treatment of the azide with palladium on carbon (0.750 g, 10 wt.%) generally according to the procedure described for Example 1 gave 5.56 g (67%) of (±)-l-(7-tert-butyl-2,3-dihydro-l-benzofuran-2- yl)methanamine as a white solid, hydrochloride salt, mp 177-180 °C (dec); Anal. Calcd. for C ₁₃ H ₁₉ NOHCl: C, 64.59; H, 8.34; N, 5.79. Found: C, 64.34; H, 9.19; N, 5.73.

Example 25: (-)-l-(7-tert-butyl-2,3-dihydro-l-benzofuran-2-yl)methanamin e

Treatment of 1.31 g of fraction 1 obtained from the chiral HPLC separation of(±)- benzyl (7-ter/-butyl-2,3 -dihydro- l-benzofuran-2-yl)methylcarbamate (Chiralcel OJ ₃ ethanol) with palladium on carbon (0.13 g, 10 wt.%) generally according to the procedure described for Example 1 gave 0.747 g (80%) of (-)-l -(7-terM>utyl-2,3 -dihydro- 1- benzofuran-2-yl)methanamine as a white solid, hydrochloride salt, [α]^ ⁵ = -25.4 (c 10.0 in methanol); mp 178-180 °C; Anal, calcd. for C ₁₃ H ₁₉ NOHCl: C, 64.59; H, 8.34; N, 5.79. Found: C, 64.23; H, 8.75; N, 5.44.

Example 26: (+)-l-(7-tert-butyl-2,3-dihydro-l-benzofuran-2-yl)methanamin e

Treatment of 2.2 g of fraction 2 obtained from the chiral HPLC separation of(±)- benzyl (7-/ert-butyl-2,3-dihydro-l-benzofuran-2-yl)methylcarbamate (Chiralcel OJ, ethanol) with palladium on carbon (0.22 g, 10 wt.%) generally according to the procedure described for Example 1 gave 1.40 g (89%) of (+)-l-(7-tert-butyl-2,3-dihydro-l- benzofuran-2-yl)methanamine as a white solid, hydrochloride salt. [OC] _D = +24.99 (c 10.0 in methanol); mp 177-179 °C; Anal, calcd. for C13H19NOHCI: C ₃ 64.59; H, 8.34; N, 5.79. Found: C, 64.87; H, 8.72; N, 5.51.

Example 27: (±)-l-(7-tert-butyl-5-chloro-2,3-dihydro-l-benzofuran-2- yl)methanamine

Treatment of (±)-(7-tert-butyl-5-chloro-2,3-dihydro-l-benzofuran-2-yl)me thyl 4- methylbenzenesulfonate (13.74 g, 34.8 mmol) with sodium azide (9.05 g, 0.139 mol) generally according to the procedure described for Intermediate 98 afforded (±)-2- (azidomethyl)-7-tert-butyl-5-chloro-2,3-dihydro-l-benzofuran . Treatment of the azide with triphenylphoshine (9.13 g, 34.8 mmol) generally according to the procedure described for Example 21 afforded 4.43 (46 of (d=)-l-(7-ført-butyl-5-chloro-2,3-dihydro-l- benzofuran-2-yl)methanamine as a white solid, hydrochloride salt, mp 229-231 °C; Anal, calcd. for C ₁₃ H ₁₈ ClNOHCl: C, 56.53; H, 6.93; N ₅ 5.07. Found: C, 56.49; H, 6.71; N, 4.86.

Example 28: (-)-l-(7-te^-butyl-5-chloro-2,3-dihydro-l-benzofuran-2- yDmethanamine

Treatment of 0.888 g of fraction 1 obtained from the (±)-benzyl (7-tør/-butyl-5- chloro-2,3-dihydro-l-benzofuran-2-yl)methylcarbamate (Chiralpak AD ₅ hexane:isopropanol 9:1) with hydrogen bromide (20 mL, 30 wt.% in acetic acid) generally according to the procedure described for Example 2 gave 0.594 g (78%) of (-)- l-(7-tert-butyl-5-chloro-2,3-dihydro-l-benzofuran-2-yl)metha namine as a white solid, hydrobromide salt. [α]o = -33.16 (c 10.0 in methanol); mp 219-222 ⁰ C; Anal, calcd. for C ₁₃ H ₁₈ ClNOHBr: C ₅ 48.69; H, 5.97; N, 4.37. Found: C ₅ 48.81; H, 6.01; N ₅ 4.24.

Example 29: (+)-l-(7-ter^-butyl-5-chloro-2,3-dihydro-l-benzofuran-2- yl)methanamine

Treatment of 0.855 g of fraction 2 obtained from the (±)-benzyl (7-fer/-butyl-5- chloro-2,3-dihydro- 1 -benzofuran-2-yl)methylcarbamate (Chiralpak AD, hexaneύsopropanol 9:1) with hydrogen bromide (20 mL, 30 wt.% in acetic acid) generally according to the procedure described for Example 2 provided 0.286 g (39%) of (+)-l-(7-tert-butyl-5-chloro-2,3-dihydro-l-benzofuran-2-yl)m ethanamine as a white solid, hydrobromide salt. [α]o = +35.32 (c 10.0 in methanol); mp 219-222 °C; Anal, calcd. for Ci ₃ Hi ₈ ClNOHBr: C, 48.69; H, 5.97; N, 4.37. Found: C, 48.78; H, 5.97; N, 4.28.

Example 30: (±)-l-(6-methoxy-2,3-dihydro-l-benzofuran-2-yl)methanamine

Treatment of (±)-(6-methoxy-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate (1.00 g, 2.99 mmol) with sodium azide (0.78 g, 11.96 mmol) generally according to the procedure described for Intermediate 98 afforded (±)-2- (azidomethyl)-6-methoxy-2,3-dihydro-l-benzofuran. Treatment of the azide with palladium on carbon (0.06 g, 10 wt.%) generally according to the procedure described for Example 1 gave 0.442 g (69%) of (±)-l-(6-methoxy-2,3-dihydro-l-benzofuran-2- yl)methanamine as a white solid, hydrochloride salt, mp > 220 ⁰ C; Anal, calcd. for CIOHI ₃ NO ₂ HCI: C, 55.69; H, 6.54; N, 6.49. Found: C ₃ 55.29; H, 6.48; N, 6.38.

Example 31 : (±)-(6-phenyl-2,3-dihydro-l-benzofuran-2-yl)methanamine

Treatment of (±)-(6-phenyl-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate (0.280 g, 0.736 mmol) with sodium azide (0.191 g, 2.94 mmol) generally according to the procedure described for Intermediate 98 gave (±)-(6-phenyl- 2,3-dihydro-l-benzofuran-2-yl)methyl azide. Treatment of the azide with palladium on carbon (0.026 g, 10 wt.%) generally according to the procedure described for Example 1 provided 0.19O g (90%) of (±)-(6-phenyl-2,3-dihydro-l-benzofuran-2-yl)methanamine as a tan solid, hydrobromide salt, mp 218-221 ⁰ C. Anal, calcd. for CisHisNOHBr: C,

58.84; H, 5.27; N, 4.57. Found: C, 54.80; H, 4.88; N, 4.18.

Example 32: (±)-l-{7-[3,5-bis(trifluoromethyl)phenyI]-2,3-dihydro-l-ben zofuran-2- yl}methanamine

Treatment of {7-[3,5-bis(trifluoromethyl)phenyl]-2,3-dihydro-l -benzofuran-2- yljmethyl 4-methylbenzenesulfonate (0.75 g, 1.45 mmol) with sodium azide (0.24 g, 3.62 mmol) generally according to the procedure described for Intermediate 98 provided (±)-2- (azidomethyl)-7-[3,5-bis(trifluoromethyl)phenyl]-2,3-dihydro -l-benzofuran. Treatment of the azide with palladium on carbon (10%, 0.075 g) generally according to the procedure described for Example 1 afforded 0.270 g (47%) of (±)-l-{7-[3,5- bis(trifluoromethyl)phenyl]-2,3-dihydro-l-benzofuran-2-yl}me thanamine as a white solid, hydrochloride salt, mp 174-175 ⁰ C (dec); Anal, calcd. for C 17H13FgNOHCl: C,

51.34; H, 3.55; N, 3.52. Found: C, 51.25; H, 3.57; N, 3.68.

Example 33: (±)-l-[7-(l-naphthyl)-2,3-dihydro-l~benzofuran-2-yI]methana mine

Treatment of (±)-(7- { [(trifluoromethyl)sulfonyl] oxy } -2,3-dihydro- 1 -benzofuran- 2-yl)methyl 4-methylbenzenesulfonate (1.5 g, 3.32 mmol) with 1-naphthaleneboronic acid (0.86 g, 4.97 mmol), tetrakis(triphenylphosphine)palladium(0) (0.38 g, 0.33 mmol), and potassium phosphate (1.41 g, 6.63 mmol) generally according to the procedure described for Intermediate 50 provided (±)-[7-(l-naphthyl)-2,3-dihydro-l-benzofuran-2- yl] methyl 4-methylbenzenesulfonate. Treatment of the tosylate with sodium azide (0.10 g, 1.49 mmol) generally according to the procedure described for Intermediate 98 afforded (±)-2-(azidomethyl)-7-(l-naphthyl)-2,3-dihydro-l-benzofuran . Treatment of the azide with palladium on carbon (0.03 g, 10 wt.%) generally according to the procedure described for Example 1 gave 0.10 g (10%) of (±)-l-[7-(l-naρhthyl)-2,3-dihydro-l- benzofuran-2-yl]methanamine as a white solid, hydrochloride salt, mp 120-124 ⁰ C; Anal. calcd. for Ci ₉ Hi ₇ NOHCl-0.5H ₂ O: C, 71.13; H, 5.97; N, 4.37. Found: C, 70.93; H, 5.74; N, 4.58.

Example 34: (±)-l-[7-(3-chloro-4-fluorophenyl)-2,3-dihydro-l-benzofuran -2- yl]methanamine Treatment of (±)-[7-(3-chloro-4-fluorophenyl)-2,3-dihydro-l-benzofuran-2 - yl]methyl 4-methylbenzenesulfonate (0.68 g, 1.57 mmol) with sodium azide (0.25 g, 3.92 mmol) generally according to the procedure described for Intermediate 98 gave (±)-2-

(azidomethyl)-7-(3-chloro-4-fluorophenyl)-2,3-dihydro-l-benz ofuran. Treatment of the azide with palladium on carbon (0.035 g, 10 wt.%) generally according to the procedure described for Example 1 afforded 0.186 g (38%) of (±)-l-[7-(3-chloro-4-fluorophenyl)- 2,3-dihydro-l-benzofuran-2-yl]methanamine as a white solid, hydrochloride salt, mp >210 °C; Anal, calcd. for C ₁₅ HI ₃ CIFNOHCI: C, 57.34; H ₅ 4.49; N, 4.46. Found: C,

57.38; H ₅ 4.32; N, 4.55.

Example 35: (±)-l-[7-(3,5-dichlorophenyl)-2,3-dihydro-l-benzofuran-2- yljmethanamme Treatment of (±)-[7-(3,5-dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]m ethyl

4-methylbenzenesulfonate (0.22 g, 0.498 mmol) with sodium azide (0.08 g, 1.25 mmol) generally according to the procedure described for Intermediate 98 afforded (±)-2- (azidomethyl)-7-(3 ₅ 5-dichlorophenyl)-2,3-dihydro-l-benzofuran. Treatment of the azide with triphenylphosphine (0.26 g, 0.997 mol) generally according to the procedure described for Example 21 afforded 0.08 g (49%) of (±)-l-[7-(3 ₅ 5-dichlorophenyl)-2,3- dihydro-l-benzofuran-2-yl]methanamine as a white solid, hydrochloride salt, mp 165-168 °C; Anal, calcd. for CI ₅ HI ₃ CI ₂ NOHCI: C, 54.49; H ₅ 4.27; N ₅ 4.24. Found: C, 54.27; H ₅

3.95; N ₅ 4.23.

Example 36: (±)-l-(7-phenyl-2,3-dihydro-l-benzofuran-2-yl)methanamine

Treatment of (±)-(7-phenyl-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate (0.40 g, 1.06 mmol) with sodium azide (0.17 g ₅ 2.65 mmol) generally according to the procedure described for Intermediate 98 provided (±)-(7- phenyl-2,3-dihydro-l-benzofuran-2-yl)methyl azide. Treatment of the azide with palladium on carbon (0.025 g, 10 wt.%) generally according to the procedure described for Example 1 afforded 0.181 g (65%) of (±)-l-(7-phenyl-2 ₅ 3-dihydro-l-benzofuran-2- yl)methanamine as a white solid, hydrochloride salt, mp >200 °C (dec); Anal, calcd. for Ci ₅ Hi ₅ NOHCl-0.2H ₂ O: C ₅ 67.90; H ₅ 6.23; N ₅ 5.28. Found: C, 67.69; H, 6.16; N, 5.3.

Example 37: (+)-(l-(7-phenyI-2,3-dihydro-l-benzofuran-2-yl)methanamine

Treatment of 0.40 g of fraction 1 obtained from the chiral HPLC separation of(±)- l-(7-phenyl-2 ₅ 3-dihydro-l-benzofuran-2-yl)methanamine (Chiralpak AD ₅ ethanol:hexane

1:1) with palladium on carbon (0.040 g, 10 wt.%) generally according to the procedure described for Example 1 gave (+)-(l-(7-phenyl-2,3-dihydro-l-benzofuran-2- yl)methanamine 0.235 g (37%) as a white solid, hydrochloride salt, [αfe ⁵ = +14.6 (c 10.0 in methanol); Anal, calcd. for C15H15NOHCI: C, 68.83; H, 6.16; N, 5.35. Found: C ₅ 67.54; H, 5.97; N, 5.03.

Example 38: (-)-l-(7-phenyI-2,3-dihydro-l-benzofuran-2-yI)methanamine

Treatment of 0.40 g of fraction 2 obtained from the chiral HPLC separation of(±)- l-(7-phenyl-2,3-dihydro-l-benzofuran-2-yl)methanamine (Chiralpak AD, ethanol:hexane 1:1) with palladium on carbon (0.040 g, 10 wt.%) generally according to the procedure described for Example 1 gave 0.212 g (33%) of (-)-l-(7-ρhenyl-2,3-dihydro-l- benzofuran-2-yl)methanamine as a white solid, hydrochloride salt, [α]^ ⁵ = -17.9 (c 10.0 in methanol); mp 220-222 °C; Anal, calcd. for Ci ₅ H ₁₅ NOHCl: C, 68.83; H, 6.16; N, 5.35.

Found: C, 67.68; H, 6.07; N, 5.15.

Example 39: (±)-l-[7-(2-naphthyl)-2,3-dihydro-l-benzofuran-2-yl]methana mine

Treatment of (±)-[7-(2-naphthyl)-2,3-dihydro-l -benzofuran-2-yl]methyl 4- methylbenzenesulfonate (0.51 g, 1.23 mmol) with sodium azide (0.20 g, 3.08 mmol) generally according to the procedure described for Intermediate 98 provided (±)-2- (azidomethyl)-7-(2-naphthyl)-2,3-dihydro-l-benzofuran. Treatment of the azide with palladium on carbon (0.050 g, 10 wt.%) generally according to the procedure described for Example 1 afforded 0.183 g (48%) of (±)-l-[7-(2-naphthyl)-2,3-dihydro-l- benzofuran-2-yl]methanamine as a white solid, hydrochloride salt, mp 135-140 ⁰ C; Anal, calcd. for C19H17NOHCIO.3H2O: C, 71.94; H, 5.91; N, 4.42. Found: C ₅ 71.67; H ₅ 5.95; N ₅ 4.25.

Example 40: (±)-l-(2',3'-dihydro-2,7'-bi-l-benzofuran-2'-yl)methanamine

Treatment of (±)-(7- { [(trifluoromethyl)sulfonyl] oxy } -2,3-dihydro- 1 -benzofuran- 2-yl)methyl 4-methylbenzenesulfonate (1.5 g, 3.32 mmol) with 2-benzofuranboronic acid (0.81 g ₅ 4.97 mmol), tetrakis(triphenylphosphine)palladium(0) (0.38 g, 0.33 mmol), and potassium phosphate (1.41 g, 6.63 mmol) generally according to the procedure described for Intermediate 50 provided (±)-2',3'-dihydro-2,7'-bi-l-benzofuran-2 ^l -ylmethyl 4-

methylbenzenesulfonate. Treatment of the tosylate with sodium azide (0.09 g, 1.32 mmol) generally according to the procedure described for Intermediate 98 afforded (±)-2'- (azidomethyl)-2',3'-dihydro-2 ₅ 7'-bi-l-benzofuran. Treatment of the azide with palladium on carbon (0.03 g, 10 wt.%) generally according to the procedure described for Example 1 provided 0.12 g (12%) of (±)-l-(2',3'-dihydro-2,7'-bi-l-benzofuran-2'-yl)methanamine as a white solid, hydrochloride salt, mp >220 ⁰ C (dec); Anal, calcd. for CI ₉ HI ₇ NOHCI-LOH ₂ O: C, 63.85; H, 5.67; N, 4.38. Found: C, 63.54; H, 5.1; N, 4.3.

Example 41 : (±)-l-[7-(3-methylphenyl)-2,3-dihydro-l-benzofuran-2- yl]methanamine

Treatment of (±)-[7-(3-methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methy l 4- methylbenzenesulfonate (0.90 g, 2.27 mmol) with sodium azide (0.44 g, 6.84 mmol) generally according to the procedure described for Intermediate 98 gave (±)-2- (azidomethyl)-7-(3-methylphenyl)-2,3-dihydro-l-benzofuran. Treatment of the azide with palladium on carbon (10%, 0.060 g) generally according to the procedure described for Example 1 afforded 0.444 g (71%) of (±)-l-[7-(3-methylphenyl)-2,3-dihydro-l- benzofuran-2-yl]methanamine as a white solid, hydrochloride salt, mp >210 °C (dec); Anal, calcd. for C ₁₆ H ₁₇ NOHCl-0.2H ₂ O: C, 68.79; H, 6.64; N, 5.01. Found: C, 68.54; H,

6.57; N, 4.9.

Example 42: (+)-l-[7-(3-methylphenyl)-2,3-dihydro-l-benzofuran-2- yl]methanamine

Treatment of 0.390 g of fraction 1 obtained from the chiral HPLC separation of(±)-benzyl [7-(3-methylphenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methylcarbamate (Chiralpak AD, ethanol:hexane 1 : 1) with palladium on carbon (0.039 g, 10 wt.%) generally according to the procedure described for Example 1 gave 0.189g (66%) of (+)- l-[7-(3-methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methanam ine as a white solid, hydrochloride salt, [α]" = +28.4 (c 10.0 in methanol); mp 196-198 °C; Anal, calcd. for CI ₆ HI ₇ NOHCI: C, 69.69; H, 6.58; N, 5.08. Found: C, 68.44; H, 6.71; N, 4.81.

Example 43: (-)-l-[7-(3-methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]meth anamine

Treatment of 0.290 g of fraction 2 obtained from the chiral HPLC separation of(±)-benzyl [7-(3-methylphenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methylcarbamate (Chiralpak AD, ethanokhexane 1:1) with palladium on carbon (0.030 g, 10 wt.%) generally according to the procedure described for Example 1 gave 0.178g (83%) of (-)-l - [7-(3-methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamin e as a white solid, hydrochloride salt, [α]" = -25.6 (c 10.0 in methanol); mp 194-196 °C; Anal, calcd. for C ₁₆ H ₁₇ NOHCl: C, 69.69; H, 6.58; N, 5.08. Found: C, 68.92; H, 6.62; N, 4.94.

Example 44: (±)-l-(7-thien-3-yl-2,3-dihydro-l-benzofuran-2-yl)methanami ne

Treatment of (±)-(7-thien-3-yl-2,3-dihydro-l -benzofuran-2-yl)methyl 4- methylbenzenesulfonate (2.2 g, 5.64 mmol) with sodium azide (1.48 g, 22.77 mmol) generally according to the procedure described for Intermediate 98 afforded (±)-(7-thien- 3-yl-2,3-dihydro-l-benzofuran-2-yl)methyl azide. Treatment of the azide with palladium on carbon (0.130 g, 10 wt.%) generally according to the procedure described for Example 1 gave 0.838 g (55%) of (±)-l-(7-thien-3-yl-2,3-dihydro-l-benzofuran-2-yl)methanami ne as a white solid, hydrochloride salt, mp >200 ⁰ C; Anal, calcd. for C ₁ 3H ₁ SFNOSHCl: C,

58.31; H, 5.27; N, 5.23. Found: C, 56.4; H, 5.23; N, 4.95.

Example 45: (+)-l-(7-thien-3-yl-2,3-dihydro-l-benzofuran-2-yl)methanamin e

Treatment of 0.219 g of fraction 1 obtained from the chiral HPLC separation of(±)-benzyl (7-thien-3-yl-2,3-dihydro- 1 -benzofuran-2-yl)methylcarbamate (Chiralcel AD ₃ wateπmethanol 1 :9) with hydrogen bromide (3.0 mL, 30 wt.% in acetic acid) generally according to the procedure described for Example 2 afforded 0.12O g (64%) of (+)-l-(7-thien-3-yl-2,3-dihydro-l-benzofuran-2-yl)methanamin eas a tan solid, hydrobromide salt, [α]" = +13.8 (c 10.0 in methanol); mp 234-236 °C; Anal, calcd. for C ₁₃ H ₁₃ NOSHBr: C, 50.01; H, 4.52; N, 4.49. Found: C, 49.37; H, 4.45; N, 4.41.

Example 46: (-)-l-(7-thien-3-yl-2,3-dihydro-l-benzofuran-2-yl)methanamin e Treatment of 0.211 g of fraction 2 obtained from the chiral HPLC separation of(±)-benzyl (7-thien-3-yl-2,3-dihydro- 1 -benzofuran-2-yl)methylcarbamate (Chiralcel AD ₅ wateπmethanol 1:9) with hydrogen bromide (3.0 mL, 30 wt.% in acetic acid)

generally according to the procedure described for Example 2 gave 0.130 g (72%) of (-)- l-(7-thien-3-yl-2,3-dihydro-l-benzofuran-2-yl)methanamine as a white solid, hydrobromide salt, [α]" = -14.5 (c 10.0 in methanol); mp 234-235 ⁰ C; Anal, calcd. for Ci ₃ Hi ₃ NOSHBr: C, 50.01; H ₅ 4.52; N, 4.49. Found: C, 49.15; H, 4.49; N, 4.38.

Example 47: (±)-l-[7-(2-methylphenyl)-2,3-dihydro-l-benzofuran-2- yl] methanamine

Treatment of (±)-[7-(2-methylρhenyl)-2,3-dihydro-l-benzofuran-2-yl]meth yl 4- methylbenzenesulfonate (7.79 g, 19.74 mmol) with sodium azide (5.13 g, 78.99 mmol) generally according to the procedure described for Intermediate 98 gave (±)-2-

(azidomethyl)-7-(2-methylphenyl)-2,3-dihydro-l-benzofuran. Treatment of the azide with palladium on carbon (0.5 g, 10 wt.%) generally according to the procedure described for Example 1 provided 3.63 g (67%) of (±)-l-[7-(2-methylphenyl)-2,3-dihydro-l- benzofuran-2-yl]methanamine as a white solid, hydrochloride salt, mp >200 °C; Anal. calcd. for CI ₆ HI ₇ NOHCI: C, 69.69; H, 6.58; N ₅ 5.08. Found: C, 69.83; H, 6.64; N, 5.

Example 48: (+)-l-[7-(2-methylphenyl)-2,3-dihydro-l-benzofuran-2- yl] methanamine

Treatment of 1.61 g of fraction 1 obtained from the chiral HPLC separation of(±)- benzyl [7-(2-methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methylcarb amate (Chiralcel OJ, ethanohhexane 1:1) with palladium on carbon (0.161 g, 10 wt.%) generally according to the procedure described for Example 1 gave 0.95 Ig (80%) of (+)-l-[7-(2- methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine as a white solid, hydrochloride salt, [α]^, ⁵ = +16.9 (c 10.0 in methanol); mp 211-212 °C; Anal, calcd. for CI ₆ HI ₇ NOHCI: C ₅ 69.69; H ₅ 6.58; N ₅ 5.08. Found: C, 68.88; H, 6.72; N ₅ 4.92.

Example 49: (-)-l-[7-(2-methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]meth anamine

Treatment of 1.68 g of fraction 2 obtained from the chiral HPLC separation of(±)- benzyl [7-(2-methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methylcarb amate (Chiralcel OJ ₅ ethanol:hexane 1 :1) with palladium on carbon (0.169 g, 10 wt.%) generally according to the procedure described for Example 1 afforded 1.04g (84%) of (-)-l-[7-(2- methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine as a white solid,

hydrochloride salt. [<X] _D = -16.4 (c 10.0 in methanol); mp 208-209 °C; Anal, calcd. for Ci ₆ H ₁₇ NOHCl: C, 69.69; H, 6.58; N ₅ 5.08. Found: C ₅ 69.19; H ₅ 6.62; N ₅ 4.91.

Example 50: (±)-l-[7-(2-fluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]met hanamine Treatment of (±)-[7-(2-fluorophenyl)-2,3-dihydro-l -benzofuran-2-yl] methyl 4- methylbenzenesulfonate (3.13 g, 7.85 mmol) with sodium azide (2.04 g, 31.42 mmol) generally according to the procedure described for Intermediate 98 afforded (±)-2- (azidomethyl)-7-(2-fluorophenyl)-2,3-dihydro-l-benzofuran. Treatment of the azide with sulfided platinum on carbon (0.21 g, 5 wt.%) generally according to the procedure described for Example 1 provided 1.81 g (83%) of (±)- 1 -[7-(2-fluorophenyl)-2 ₅ 3-dihydro- l-benzofuran-2-yl]methanamine as a white solid, hydrochloride salt, mp 244-246 ⁰ C; Anal, calcd. for C15H14FNOHCI: C ₅ 64.4; H ₅ 5.4; N ₅ 5.01. Found: C ₅ 63.98; H, 5.4; N ₅

4.89.

Example 51: (+)-l-[7-(2-fluorophenyl)-2,3-dihydiO-l-benzofuran-2-yl]meth anamine

Treatment of 0.542 g of fraction 1 obtained from the chiral HPLC separation of(±)-benzyl [7-(2-fluorophenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methylcarbamate (Chiralcel OJ, hexane:isopropanol 9:1) with palladium on carbon (0.054 g, 10 wt.%) generally according to the procedure described for Example 1 gave 0.337 g (84%) of (+)- l-[7-(2-fluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methanam ine as a white solid, hydrochloride salt. [<X] _D = +7.14 (c 10.0 in dimethylsulfoxide); mp 227-228 °C; Anal, calcd. for C15H14FNOHCI: C ₅ 64.4; H ₅ 5.4; N ₅ 5.01. Found: C ₅ 63.96; H ₅ 5.4; N ₅ 4.84.

Example 52: (-)-l-[7-(2-fluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]meth anamine Treatment of 0.509 g of fraction 2 obtained from the chiral HPLC separation of(±)-benzyl [7-(2-fluorophenyl)-2 ₅ 3-dihydro- 1 -benzofuran-2-yl]methylcarbamate (Chiralcel OJ ₅ hexane:isopropanol 9:1) with palladium on carbon (0.050 g, 10 wt.%) generally according to the procedure described for Example 1 provided 0.318g (84%) of (-)-l-[7-(2-fluorophenyl)-2 ₅ 3-dihydro-l-benzofuran-2-yl]methanamine as a white solid, hydrochloride salt, [α]" - -9.48 (c 10.0 in dimethylsulfoxide); mp 224-225 °C; Anal, calcd. for C ₁₅ Hi ₄ FNOHCl: C ₅ 64.4; H ₅ 5.4; N ₅ 5.01. Found: C ₅ 63.74; H ₅ 5.21; N ₅ 4.91.

Example 53: (±)-l-{7-[2-(trifluoromethyl)phenyl]-2,3-dihydro-l-benzofur an-2- yl}methanamine

Treatment of (7-bromo-2,3-dihydro-l-beiizofuran-2-yl)methyl A- methylbenzenesulfonate (4.0 g, 10.44 mmol) with 2-(trifluoromethyl)phenylboronic acid (2.57 g, 13.6 mmol), dichlorobis(tri-o-tolylphosphine)-palladium(II) (0.426 g, 0. 542 mmol), and potassium carbonate (3.61 g, 26.09 mmol) generally according to the procedure described for Intermediate 37 provided (±)-{7-[2-(trifluoromethyl)phenyl]-2,3- dihydro-l-benzofuran-2-yl}methyl 4-methylbenzenesulfonate. Treatment of the tosylate with sodium azide (1.31 g, 20.25 mmol) generally according to the procedure described for Intermediate 98 afforded (±)-2-(azidomethyl)-7-[2-(trifluoromethyl)phenyl]-2,3- dihydro-1-benzofuran. Treatment of the azide with palladium on carbon (0.160 g, 10 wt.%) generally according to the procedure described for Example 1 provided 1.05 g (65%) of (±)-l-{7-[2-(trifluoromethyl)phenyl]-2,3-dihydro-l-benzofur an-2- yl}methanamine as a white solid, hydrochloride salt, mp 204-205 ⁰ C; Anal, calcd. for C16H14F3NOHCI: C, 58.25; H, 4.59; N, 4.25. Found: C, 57.57; H, 4.52; N, 4.08.

Example 54: (-)-l-{7-[2-(trifluoromethyl)phenyl]-2,3-dihydro-l-benzofura n-2- yl}methanamine Treatment of 0.350 g of fraction 1 obtained from the chiral HPLC separation of(±)-benzyl {7-[2-(trifluoromethyl)phenyl]-2,3-dihydro-l-benzofuran-2- yl}methylcarbamate (Chiralcel OJ, ethanol:hexane 1 :1) with palladium on carbon (0.035 g, 10 wt.%) generally according to the procedure described for Example 1 gave 0.200 g (74%) of (-)-l-{7-[2-(trifluoromethyl)phenyl]-2,3-dihydro-l-benzofura n-2- yljmethanamine as a white solid, hydrochloride salt, [α]^ ⁵ = -23.10 (c 10.0 in methanol); mp 109-111 °C; Anal, calcd. for C ₁₆ HHF ₃ NOHCI: C ₅ 58.28; H ₃ 4.59; N, 4.25. Found: C, 58.09; H, 4.35; N, 4.21.

Example 55: (+)-l-{7-[2-(trifluoromethyl)phenyl]-2,3-dihydro-l-benzofura n-2- yljmetlianamine

Treatment of 0.343 g of fraction 2 obtained from the chiral HPLC separation of(±)-benzyl {7-[2-(trifluoromethyl)phenyl]-2,3-dihydro-l-benzofuran-2-

yl}methylcarbamate (Chiralcel OJ, ethanokhexane 1:1) with palladium on carbon (0.034 g, 10 wt.%) generally according to the procedure described for Example 1 provided 0.165 g (62%) of (+)-l-{7-[2-(trifluoromethyl)phenyl]-2,3-dihydro-l-benzofura n-2- yl}methanamine as a white solid, hydrochloride salt, [α]^ ^{5 =} +25.12 (c 10.0 in methanol); mp 97-100 ⁰ C; Anal, calcd. for C16H14F3NOHCI: C, 58.28; H, 4.59; N ₅ 4.25. Found: C, 57.82; H ₅ 4.35; N, 4.15.

Example 56: (±)-l-[7-(2,6-dimethylphenyl)-2,3-dihydro-l-benzofuran-2- yljmethanamine Treatment of (±)-[7-(2,6-dimethylphenyl)-2,3-dihydro-l-benzofuran-2-yl]m ethyl

4-methylbenzenesulfonate (0.646 g, 1.58 mmol) with sodium azide (0.411 g, 6.33 mmol) generally according to the procedure described for Intermediate 98 afforded (±)-2- (azidomethyl)-7-(2,6-dimethylphenyl)-2,3-dihydro-l-benzofura n. Treatment of the azide with palladium on carbon (0.057 g, 10 wt.%) generally according to the procedure described for Example 1 provided 0.383g (84%) of (±)-l -[7-(2,6-dimethylphenyl)-2,3- dihydro-l-benzofuran-2-yl]methanamine as a white solid, hydrochloride salt, mp >250 ⁰ C; Anal, calcd. for C ₁₇ Hi ₉ NOHCl: C, 70.46; H, 6.96; N ₅ 4.83. Found: C, 69.06; H,

7.01; N, 4.21.

Example 57: (-)-l-[7-(2,6-dimethylphenyl)-2,3-dihydro-l-benzofuran-2- yljmethanamine

Treatment of 0.524 g of fraction 1 obtained from the chiral HPLC separation of(±)-benzyl [7-(2,6-dimethylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl carbamate (Chiralcel OJ, methanol: carbon dioxide 3:7) with palladium on carbon (0.052 g, 10 wt.%) generally according to the procedure described for Example 1 gave 0.183 g (47%) of (-)- l-[7-(2,6-dimethylphenyl)-2,3-dihydro-l-benzofuran-2-yl]meth anamine as a white solid, hydrochloride salt, [aft ⁵ = -3.98 (c 10.0 in methanol); mp 244-247 ⁰ C; Anal, calcd. for C ₁₇ Hi ₉ NOHCl: C, 70.46; H, 6.96; N, 4.83. Found: C ₅ 69.61; H ₅ 7.00; N ₅ 4.60.

Example 58: (+)-l-[7-(2,6-dimethylphenyl)-2,3-dihydro-l-benzofuran-2- yl] methanamme

Treatment of 0.530 g of fraction 2 obtained from the chiral HPLC separation of(±)-benzyl [7-(2,6-dimethylphenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methylcarbamate (Chiralcel OJ, methanol: carbon dioxide 3:7) with palladium on carbon (0.053 g, 10 wt.%) generally according to the procedure described for Example 1 afforded 0.224g (57%) of (+)-l-[7-(2,6-dimethylphenyl)-2,3-dihydro-l-benzofuran-2-yl] methanamine as a white solid, hydrochloride salt, [α]^ ⁵ = +4.28 (c 10.0 in methanol); mp 244-247 ⁰ C; Anal, calcd. for C17H19NOHCI: C, 70.46; H ₅ 6.96; N ₅ 4.83. Found: C, 69.61; H, 6.87; N ₅ 4.65.

Example 59: (±)-l-[7-(2-methoxyphenyI)-2,3-dihydro-l-benzofuran-2- yljmethanamine

Treatment of (±)-(7-bromo-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate (5.0 g, 13.05 mmol) with 2-methoxyphenylboronic acid (2.57 g, 16.96 mmol), dichlorobis(tri-o-tolylphosphine)-palladium(II) (0.532 g, 0. 677 mmol), and potassium carbonate (4.51 g, 32.62 mmol) generally according to the procedure described for Intermediate 37 provided (±)-[7-(2-methoxyphenyl)-2,3-dmydro~l-benzofuran-2~ yljmethyl 4-methylbenzenesulfonate. Treatment of the tosylate with sodium azide (0.76 g, 11.69 mmol) generally according to the procedure described for Intermediate 98 gave (±)-2-(azidomethyl)-7-(2-methoxyρhenyl)-2,3-dihydro- 1 -benzofuran. Treatment of the azide with palladium on carbon (0.072 g, 10 wt.%) generally according to the procedure described for Example 1 provided 0.453 g (12%) of (±)-l-[7-(2-methoxyphenyl)-2,3- dihydro-l-benzofuran-2-yl]methanamine as a white solid, hydrochloride salt, mp >250 °C; Anal, calcd. for CI ₆ HI ₇ NO ₂ HCI: C ₅ 65.86; H ₅ 6.22; N ₅ 4.8. Found: C, 65.72; H ₅

6.15; N ₅ 4.86.

Example 60: (±)-l-[7-(2-chlorophenyI)-2,3-dihydro-l-benzofuran-2-yl]met hanamine

Treatment of (±)- [7-(2-chlorophenyl)-2,3 -dihydro- 1 -benzofuran-2-yl]methyl 4- methylbenzenesulfonate (2.6 g, 6.26 mmol) with sodium azide (1.63 g, 25.05 mmol) generally according to the procedure described for Intermediate 98 gave (±)-2- (azidomethyl)-7-(2-chlorophenyl)-2,3-dihydro-l -benzofuran. Treatment of the azide with sulfided platinum on carbon (0.17 g, 5 wt.%) generally according to the procedure described for Example 1 provided 1.05 g (57%) of (±)-l-[7-(2-chlorophenyl)-2,3-dihydro- l-benzofuran-2 -yljmethanamine as a white solid, hydrochloride salt, mp >250 °C; Anal.

calcd. for C15H14CINOHCI: C ₅ 60.83; H, 5.1; N, 4.73. Found: C, 60.71; H, 5.48; N, 4.55.

Example 61: (±)-[7-(2-isopropylphenyI)-2,3-dihydro-l-benzofuran-2- yljmethylamme

Treatment of (±)-(7-bromo-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate (4.81 g, 12.56 mmol) with 2-(2-isopropylphenyl)-4,4,5,5- tetramethyl-l,3,2-dioxaborolane (4.63 g, 18.84 mmol, Intermediate 35), dichlorobis(tri-o- tolylphosphine)-palladium(II) (0.493 g, 0.627 mmol), and potassium carbonate (4.34 g, 31.38 mmol) generally according to the procedure described for Intermediate 37 provided (±)-[7-(2-isopropylphenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methyl 4- methylbenzenesulfonate. Treatment of the tosylate with sodium azide (2.10 g, 32.37 mmol) generally according to the procedure described for Intermediate 98 provided (±)-2- (azidomethyl)-7-(2-isopropylphenyl)-2,3-dihydro-l-benzofuran . Treatment of the azide with palladium on carbon (0.22 g, 10 wt.%) generally according to the procedure described for Example 1 provided 2.15 g (56%) of (±)-[7-(2-isopropylphenyl)-2,3- dihydro-l-benzofuran-2-yl]methylamine as a white solid, hydrochloride salt, mp 202-204 °C; Anal, calcd. for Ci ₈ H ₂ INOHCl: C, 71.16; H, 7.30; N, 4.61. Found: C, 70.83; H,

7.34; N, 4.48.

Example 62: (+)-[7-(2-isopropyIphenyl)-2,3-dihydro-l-benzofuran-2- yl]methylamine

Treatment of 0.760 g of fraction 1 obtained from the chiral HPLC separation of(±)-benzyl [7-(2-isopropylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methylc arbamate (Chiralcel OD, hexane:isopropanol 9:1) with palladium on carbon (0.076 g, 10 wt.%) generally according to the procedure described for Example 1 gave 0.388 g (63%) of (+)- [7-(2-isopropylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyla mine as a white solid, hydrochloride salt, [άffi = +15.7 (c 10.0 in methanol); mp 205-206 ⁰ C; Anal, calcd. for Ci ₈ H ₂ INOHCl: C, 71.16; H, 7.3; N, 4.61. Found: C, 70.78; H, 7.42; N, 4.47.

Example 63: (-)-[7-(2-isopropylphenyl)-2,3-dihydro-l-benzofuran-2-yl]met hylamine

Treatment of 0.749 g of fraction 2 obtained from the chiral HPLC separation of(±)-benzyl [7-(2-isopropylphenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methylcarbamate (Chiralcel OD, hexane:isopropanol 9:1) with palladium on carbon (0.075 g, 10 wt.%) generally according to the procedure described for Example 1 provided 0.376g (66%) of (-)-[7-(2-isopropylphenyl)-2,3-dihydro-l-benzofuran-2-yl]met hylamine as a white solid, hydrochloride salt, [α]" = -16.0 (c 10.0 in methanol); mp 205-206 °C; Anal, calcd. for Ci ₈ H ₂ INOHCl: C, 71.16; H ₅ 7.3; N, 4.61. Found: C, 70.54; H, 7.37; N, 4.61.

Example 64: (±)-l-[7-(3-fluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]met hanamine

Treatment of (±)-[7-(3-fluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methy l 4- methylbenzenesulfonate (1.68 g, 4.22 mmol) with sodium azide (1.09 g, 16.88 mmol) generally according to the procedure described for Intermediate 98 afforded (±)-2- (azidomethyl)-7-(3-fluorophenyl)-2,3-dihydro-l-benzofuran. Treatment of the azide with palladium on carbon (0.107 g, 10 wt.%) generally according to the procedure described for Example 1 provided 0.95 g (81%) of (±)-l-[7-(3-fluorophenyl)-2,3-dihydro-l- benzofuran-2-yl]methanamine as a white solid, hydrochloride salt, mp 200-202 °C, Anal, calcd. for Ci ₅ H ₁₄ FNOHCl: C, 64.4; H, 5.4; N, 5.01. Found: C, 63.93; H, 5.48; N, 4.73.

Example 65: (±)-l-[7-(3-chIorophenyl)-2,3-dihydro-l-benzofuran-2-yl]met hanamine

Treatment of (±)-[7-(3-chlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methy l 4- methylbenzenesulfonate (3.6 g, 8.66 mmol) with sodium azide (2.25 g, 34.65 mmol) generally according to the procedure described for Intermediate 98 gave (±)-2- (azidomethyl)-7-(3-chlorophenyl)-2,3-dihydro-l-benzofuran. Treatment of the azide with sulfided platinum on carbon (0.125 g, 5 wt.%) generally according to the procedure described for Example 1 provided 1.91 g (74%) of (±)-l-[7-(3-chlorophenyl)-2,3-dihydro- l-benzofuran-2-yl]methanamine as a tan solid, hydrochloride salt, mp 150-154 °C; Anal, calcd. for C15H14CINOHCI: C, 60.83; H, 5.1; N, 4.73. Found: C, 59.17; H, 5.12; N,

4.38.

Example 66: (+)-l-[7-(3-chlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]meth anamine

Treatment of 0.495 g of fraction 1 obtained from the chiral HPLC separation of(±)-benzyl [7-(3-chlorophenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methylcarbamate (Chiralpak AS, hexaneύsopropanol 9:1) with hydrogen bromide (6.2 mL, 30 wt.% in acetic acid) generally according to the procedure described for Example 2 gave 0.150g (28%) of (+)-l-[7-(3-chlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]meth anamine as a tan solid, hydrobromide salt. [<X] _D = +35.7 (c 10.0 in methanol); mp 187-189 ⁰ C; Anal, calcd. for C ₁₅ Hi ₄ ClNOHBr: C.52.89; H, 4.44; N, 4.11. Found: C, 52.4; H, 4.47; N, 3.97.

Example 67: (-)-l-[7-(3-chIorophenyl)-2,3-dihydro-l-benzofuran-2-yl]meth anamine Treatment of 0.542 g of fraction 2 obtained from the chiral HPLC separation of(±)-benzyl [7-(3-chlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methylcarb amate (Chiralpak AS, hexaneasopropanol 9: 1) with hydrogen bromide (6.8 mL, 30 wt.% in acetic acid) generally according to the procedure described for Example 2 afforded 0.232 g (49%) of (-)-l-[7-(3-chlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]meth anamine as a white solid, hydrobromide salt. [α]o = -34.6 (c 10.0 in methanol); mp 189-190 ⁰ C; Anal, calcd. for Ci ₅ H ₁₄ ClNOHBr: C, 52.89; H, 4.44; N, 4.11. Found: C, 52.83; H, 4.47; N, 3.97.

Example 68: (±)-l-[7-(3-methoxyphenyl)-2,3-dihydro-l-benzofuran-2- yljmethanamine

Treatment of (±)-[7-(3-methoxyphenyl)-2,3-dihydro-l-benzofuran-2-yl]meth yl 4- methylbenzenesulfonate (3.0 g, 7.82 mmol) with sodium azide (0.309 g, 4.48 mmol) generally according to the procedure described for Intermediate 98 gave (±)-2- (azidomethyl)-7-(3-methoxyphenyl)-2,3-dihydro-l-benzofuran. Treatment of the azide with palladium on carbon (0.030 g, 10 wt.%) generally according to the procedure described for Example 1 provided 0.25 g (80%) of (±)-l-[7-(3-methoxyρhenyl)-2,3~ dihydro-l-benzofuran-2 -yljmethanamine as a white solid, hydrochloride salt, mp 152-154 ⁰ C; Anal, calcd. for C16H17NO2HCI: C, 65.86; H, 6.22; N, 4.8. Found: C, 65.21; H,

6.17; N, 4.46.

Example 69: (±)-l-{7-[3-(trifluoromethyl)phenyl]-2,3-dihydro-l-benzofur an-2- yl}methanamine

Treatment of (±)-{7-[3-(trifluoromethyl)phenyl]-2,3-dihydro-l-benzofuran -2- yl}methyl 4-methylbenzenesulfonate (5.2 g, 11.57 mmol) with sodium azide (3.01 g, 46.3 mmol) generally according to the procedure described for Intermediate 98 gave (±)-2- (azidomethyl)-7-[3-(trifluoromethyl)phenyl]-2,3-dihydro-l -benzofuran. Treatment of the azide with palladium on carbon (0.375 g, 10 wt.%) generally according to the procedure described for Example 1 provided 2.64 g (69%) of (±)-l-{7-[3-(trifluoromethyl)phenyl]- 2,3-dihydro-l-benzofuran-2-yl}methanamine as a white solid, hydrochloride salt, mp 172-174 ⁰ C; Anal, calcd. for C ₁₆ H ₁₄ F ₃ NOHCl: C, 58.28; H, 4.59; N, 4.25. Found: C,

58.09; H, 4.6; N, 4.03.

Example 70: (±)-l-[7-(4-methylphenyl)-2,3-dihydro-l-benzofuran-2- yl]methanamine

Treatment of (±)-[7-(4-methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methy l 4- methylbenzenesulfonate (1.01 g, 2.56 mmol) with sodium azide (0.664 g, 10.24 mmol) generally according to the procedure described for Intermediate 98 gave (±)-2-

(azidomethyl)-7-(4-methylphenyl)-2,3-dihydro-l -benzofuran. Treatment of the azide with palladium on carbon (0.03 g, 10 wt.%) generally according to the procedure described for Example 1 provided 0.528 g (75%) of (±)-l-[7-(4-methylphenyl)-2,3-dihydro-l- benzofuran-2-yl]methanamine as a white solid, hydrochloride salt, mp 231-232 °C; Anal. calcd. for C ₁₆ H ₁₇ NOHCl: C, 69.69; H, 6.58; N, 5.08. Found: C, 66.26; H, 7.0; N, 4.73.

Example 71 : (+)-l-[7-(4-methylphenyl)~2,3-dihydro-l-benzofuran-2- yl]methanamine

Treatment of 0.198 g of fraction 1 obtained from the chiral HPLC separation of(±)-benzyl [7-(4-methylphenyl)-2,3-dihydro-l -benzofuran-2-yl]methylcarbamate (Chiralpak AD, methanol: water 19:1) ) with hydrogen bromide (3.0 mL, 30 wt.% in acetic acid) generally according to the procedure described for Example 2 afforded 0.143 g (84%) of (+)-l-[7-(4-methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]meth anamine as a tan solid, hydrobromide salt, [α]^ ⁵ = +17.42 (c 10.0 in methanol); mp >250 °C; Anal. calcd. for C ₁₆ H ₁₇ NOHBr: C, 60.01; H, 5.67; N, 4.37. Found: C, 59.58; H, 5.57; N, 4.26.

Example 72: (-)-l-[7-(4-methylphenyl)-2,3-dihydro-l-benzofuran-2-yI]meth anamine

Treatment of 0.167 g of fraction 2 obtained from the chiral HPLC separation of(±)-benzyl [7-(4-methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methylcarb amate (Chiralpak AD ₅ methanol: water 19:1) with hydrogen bromide (3.0 mL, 30 wt.% in acetic acid) generally according to the procedure described for Example 2 gave 0.067 g (47%) of (-)-l-[7-(4-methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]meth anamine as a white solid, hydrobromide salt. [a]p = -17.02 (c 10.0 in methanol); mp >250 °C; Anal, calcd. for Ci^H ₁₇ NOHBr: C, 60.01; H ₅ 5.67; N, 4.37. Found: C ₅ 59.5; H ₅ 5.67; N, 4.23.

Example 73: (±)-l-[7-(4-fluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]met hanamine

Treatment of (±)-[7-(4-fluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methy l 4- methylbenzenesulfonate (1.1 g, 3.01 mmol) with sodium azide (0.784 g, 12.04 mmol) generally according to the procedure described for Intermediate 98 afforded (±)-2- (azidomethyl)-7-(4-fluorophenyl)-2,3-dihydro-l-benzofuran. Treatment of the azide with palladium on carbon (0.074 g, 10 wt.%) generally according to the procedure described for Example 1 provided 0.542 g (64%) of (±)-l-[7-(4-fluorophenyl)-2,3-dihydro-l- benzofuran-2-yl]methanamine as a white solid, hydrochloride salt, mp 237-240 °C; Anal, calcd. for C15H14FNOHCI: C, 64.4; H, 5.4; N ₅ 5.01. Found: C, 64.26; H, 5.33; N, 4.85.

Example 74: (+)-!- [7-(4-fluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamin e

Treatment of 0.184 g of fraction 1 obtained from the chiral HPLC separation of(±)-benzyl [7-(4-fluorophenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methylcarbamate (Chiralcel OD, methanol:water 19:1) with hydrogen bromide (2.0 mL, 30 wt.% in acetic acid) generally according to the procedure described for Example 2 gave 0.08 g (55%) of (+)-l-[7-(4-fluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]meth anamine as a white solid, hydrobromide salt. [α]p ⁵ = +13.26 (c 10.0 in methanol); mp 207-208 °C; Anal, calcd. for C ₁₅ H^FNOHBr: C, 55.57; H ₅ 4.66; N ₅ 4.32. Found: C, 55.10; H ₅ 4.59; N ₅ 4.22.

Example 75: (-)-l-[7-(4-fluorophenyI)-2,3-dihydro-l-benzofuran-2-yl]meth anamine Treatment of 0.173 g of fraction 2 obtained from the chiral HPLC separation of(±)-benzyl [7-(4-fluorophenyl)-2,3 -dihydro- 1 -benzofuran-2-yl]methylcarbamate (Chiralcel OD, methanol:water 19:1) with hydrogen bromide (2.0 mL, 30 wt.% in acetic

acid) generally according to the procedure described for Example 2 provided 0.108 g (73%) of (-)-l-[7-(4-fluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]meth anamine as a white solid, hydrobromide salt. [α]o = -12.24 (c 10.0 in methanol); mp 208-210 °C; Anal, calcd. for Ci ₅ H ₁₄ FNOHBr: C, 55.57; H, 4.66; N, 4.32. Found: C, 55.12; H, 4.62; N, 4.21.

Example 76: (±)-l-[7-(4-chlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]met hanamine

Treatment of (±)-[7-(4-chlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methy l 4- methylbenzenesulfonate (1.2 g, 2.89 mmol) with sodium azide (0.752 g, 11.57 mmol) generally according to the procedure described for Intermediate 98 afforded (±)-2-

(azidomethyl)-7-(4-fluorophenyl)-2,3-dihydro-l-benzofuran. Treatment of the azide with sulfided platinum on carbon (0.082 g, 5 wt.%) generally according to the procedure described for Example 1 provided 0.592 g (69%) of (±)-l-[7-(4-chlorophenyl)-2,3- dihydro-l-benzofuran-2-yl]methanamine as a white solid, hydrochloride salt, mp 212-214 ⁰ C; Anal, calcd. for CI ₅ H ₁₄ CINOHCI: C, 60.83; H, 65.10; N, 4.73. Found: C, 59.99; H,

5.00; N, 4.47.

Example 77: (+)-l-[7-(4-chlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]meth anamine

Treatment of 0.226 g of fraction 1 obtained from the chiral HPLC separation of(±)-benzyl [7-(4-chlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methylcarb amate (Chiralcel AD, methanol) with hydrogen bromide (5.7 mL, 30 wt.% in acetic acid) generally according to the procedure described for Example 2 gave 0.113 g (58%) of (+)- l-[7-(4-chlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methanam ine as a white solid, hydrobromide salt. [α]n = +15.72 (c 10.0 in methanol); mp 229-231 °C; Anal, calcd. for C ₁₅ H ₁₄ ClNOHBr: C, 52.89; H, 4.44; N, 4.11. Found: C, 52.98; H, 4.43; N, 4.05.

Example 78: (-)-l-[7-(4-chlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]meth anamine

Treatment of 0.229 g of fraction 2 obtained from the chiral HPLC separation of(±)-benzyl [7-(4-chlorophenyl)-2,3 -dihydro- 1 -benzofuran-2-yl]methylcarbamate (Chiralcel AD, methanol) with hydrogen bromide (5.8 mL, 30 wt.% in acetic acid) generally according to the procedure described for Example 2 provided 0.121 g (61%) of

(-)-l-[7-(4-chlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]m ethanamine as a white solid,

hydrobromide salt. [α]β = -18.40 (c 10.0 in methanol); mp 233-235 °C; Anal, calcd. for Ci ₅ Hi4ClNOHBr: C, 52.89; H, 4.44; N ₅ 4.11. Found: C, 52.78; H, 4.4; N, 3.98.

Example 79: (±)-l-[7-(4-methoxyphenyl)-2,3-dihydro-l-benzofuran-2- yljmethanamine

Treatment of (±)-[7-(4-methoxyphenyl)-2,3-dihydro-l-benzofuran-2-yl]meth yl A- methylbenzenesulfonate (2.1g, 5.11 mmol) with sodium azide (1.33 g, 20.96 mmol) generally according to the procedure described for Intermediate 98 afforded (±)-2- (azidomethyl)-7-(4-methoxyphenyl)-2,3-dihydro-l-benzofuran. Treatment of the azide with palladium on carbon (0.125 g, 10 wt.%) generally according to the procedure described for Example 1 provided 0.860 g (58%) of (±)-l-[7-(4-methoxyphenyl)-2,3- dihydro-l-benzofuran-2-yl]methanamine as a white solid, hydrochloride salt, mp 176-178 °C; Anal, calcd. for CiOH ₁₇ NO ₂ HCl: C, 65.86; H, 6.22; N, 4.80. Found: C, 65.02; H,

6.13; N, 4.57.

Example 80: (+)-l-[7-(4-methoxyphenyl)-2,3-dihydro-l~benzofuran-2- yl]methanamine

Treatment of 0.314 g of fraction 1 obtained from the chiral HPLC separation of(±)-benzyl [7-(4-methoxyphenyl)-2,3-dihydro-l-benzofuran-2-yl]methylcar bamate (Chiralcel AD, methanol) with palladium on carbon (0.031 g, 10 wt.%) generally according to the procedure described for Example 1 provided 0.16Og (68%) of (+)-l-[7- (4-methoxyphenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine as a white solid, hydrochloride salt, [α]" = +20.34 (c 10.0 in methanol); mp 183-186 °C; Anal, calcd. for Ci6H ₁₇ NO ₂ HCl: C, 65.86; H, 6.22; N, 4.8. Found: C, 62.45; H, 6.11; N, 4.38.

Example 81: (-)-l-[7-(4-methoxyphenyl)-2,3-dihydro-l-benzofuran-2- yl]methanamine

Treatment of 0.312 g of fraction 2 obtained from the chiral HPLC separation of(±)-benzyl [7-(4-methoxyphenyl)-2,3-dihydro-l -benzofuran-2-yl]methylcarbamate with hydrogen bromide (12.0 mL, 30 wt.% in acetic acid) generally according to the procedure described for Example 2 provided 0.156 g (58%) of (-)-l-[7-(4-methoxyρhenyl)-2,3- dihydro-l-benzofuran-2-yl]methanamine as a white solid, hydrobromide salt. [α]o ⁵ = -

14.66 (c 10.0 in methanol); mp 185-188 ⁰ C; Anal, calcd. for Ci _β HiγNC^HBr: C, 57.16; H, 5.4; N, 4.17. Found: C ₃ 56.53; H, 5.48; N, 4.01.

Example 82: (±)-l-{7-[4-(trifluoromethyl)phenyI]-2,3-dihydro-l-benzofur an-2- yl}methanamine

Treatment of (±)-{7-[4-(trifluoromethyl)phenyl]-2,3-dihydro-l-benzoforan -2- yl}methyl 4-methylbenzenesulfonate (3.3 g, 7.34 mmol) with sodium azide (1.91 g, 29.38 mmol) generally according to the procedure described for Intermediate 98 gave (±)-2- (azidomethyl)-7-[4-(trifluoromethyl)phenyl]-2,3-dihydro-l -benzofuran. Treatment of the azide with palladium on carbon (0.205 g, 10 wt.%) generally according to the procedure described for Example 1 provided 1.82 g (75%) of (±)-l-{7-[4-(trifluoromethyl)phenyl]- 2,3-dihydro-l-benzofuran-2-yl}methanamine as a white solid, hydrochloride salt, mp >250 ⁰ C; Anal, calcd. for CI ₆ HI ₄ F ₃ NOHCI: C, 58.28; H, 4.59; N, 4.25. Found: C,

57.47; H, 4.82; N, 3.65.

Example 83: (±)-l-[7-(2,4-dichlorophenyl)-2,3-dihydro-l-benzofuran-2- yljmethanamine

Treatment of (±)-[7-(2,4-dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]m ethyl 4-methylbenzenesulfonate (4.2 g, 9.34 mmol) with sodium azide (2.4 g, 37.38 mmol) generally according to the procedure described for Intermediate 98 gave (±)-2-

(azidomethyl)-7-(2,4-dichlorophenyl)-2,3-dihydro-l -benzofuran. Treatment of the azide with sulfided platinum on carbon (0.32 g, 5 wt.%) generally according to the procedure described for Example 1 provided 2.16 g (72%) of (±)-l-[7-(2,4-dichlorophenyl)-2,3- dihydro-l-benzofuran-2-yl]methanamine as a white solid, hydrochloride salt, mp 198-200 °C; Anal, calcd. for C _{1 5} HI ₃ CI ₂ NOHCI: C, 54.49; H, 4.27; N ₅ 4.24. Found: C, 54.5; H,

4.39; N, 4.16.

Example 84: (±)-l-(5-chloro-7-phenyl-2,3-dihydro-l-benzofuran-2-yl)meth anamine

Treatment of (±)-(5-chloro-7-phenyl-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate (0.55 g, 1.33 mmol) with sodium azide (0.345 g, 5.31 mmol) generally according to the procedure described for Intermediate 98 provided 0.35 g of (±)-2-(azidomethyl)-5-chloro-7-phenyl-2,3-dihydro-l -benzofuran as a colorless oil.

Treatment of the azide with sulfided platinum on carbon (90 mg, 5 wt.%) generally according to the procedure described for Example 1 provided 0.14 g (40%) of (±)-l-(5- chloro-7-phenyl-2,3-dihydro-l-benzofuran-2-yl)methanamine as a white solid, hydrochloride salt, mp 258 ⁰ C (dec); Anal, calcd. for C15H14CINOHCI: C, 60.83; H, 5.1; N, 4.73. Found: C, 60.13; H, 4.95; N, 4.6.

Example 85: (+)-l-(5-chloro-7-phenyl-2,3-dihydro-l-benzofuran-2-yI)metha namine

Treatment of (±)-l-(5-chloro-7-phenyl-2,3-dihydro-l-benzofuran-2- yl)methanamine (0.8 g, 2.70 mmol) with diisopropylethylamine (1.05 g, 8.10) and benzyl chloroformate (0.83 g, 4.86 mmol) generally according to the procedure described for Intermediate 12 afforded (±)-benzyl (5-chloro-7-phenyl-2,3-dihydro-l-benzofuran-2- yl)methylcarbamate. Chiral HPLC separation of (±)-benzyl (5-chloro-7-phenyl-2,3- dihydro-l-benzofuran-2-yl)methylcarbamate (Chiralpak AD, ethanol) provided two fractions. Fraction 1 (R _t = 10.875 min, (Chiralpak AD, ethanol); Fraction 2 (R _t = 15.590 min, (Chiralpak AD, ethanol). Treatment of 0.40 g of fraction 1 obtained from the chiral HPLC separation of(±)-benzyl (5-chloro-7-phenyl-2,3-dihydro-l-benzofuran-2- yl)methylcarbamate (Chiralpak AD, ethanol) with hydrogen bromide (5 mL, 30 wt.% in acetic acid) generally according to the procedure described for Example 2 gave 0.27 g (77%) of (+)-l-(5-chloro-7-phenyl-2,3-dihydro-l-benzofuran-2-yl)metha namine as a white solid, hydrobromide salt. [α]" = +0.7 (c 10.0 in methanol); mp 201-203 °C; Anal, calcd. for C 15H14ClNOHBr: C, 52.89; H, 4.44; N, 4.11. Found: C, 52.96; H, 4.25; N, 3.88.

Example 86: (-)-l-(5-chloro-7-phenyl-2,3-dihydro-l-benzofuran-2-yl)metha namine Treatment of 0.23 g of fraction 2 obtained from the chiral HPLC separation of(±)- benzyl (5-chloro-7-phenyl-2,3-dihydro-l-benzofuran-2-yl)methylcarba mate (Chiralpak AD, ethanol) with hydrogen bromide (3 mL, 30 wt.% in acetic acid) generally according to the procedure described for Example 2 gave 0.14 g (70%) of (-)-l-(5-chloro-7-phenyl- 2,3-dihydro-l-benzofuran-2-yl)methanamine as a white solid, hydrobromide salt, [α]^, ⁵ = -0.6 (c 10.0 in methanol); mp 201-203 °C; Anal, calcd. for Ci ₅ HHClNOHBr: C, 52.89; H, 4.44; N, 4.11. Found: C, 52.76; H, 4.38; N ₅ 4.06.

Example 87: (±)-l-[5-chloro-7-(2-chloropheuyl)-2,3-dihydro-l-benzofuran -2- yl]methanamine

Treatment of (±)-(5 -chloro-7- { [(trifluoromethyl)sulfonyl] oxy } -2,3-dihydro- 1 - benzofuran-2-yl)methyl 4-methylbenzenesulfonate (1.40 g, 2.88 mmol) with 2- chlorophenylboronic acid (0.67 g, 1.49 mmol), dichloro[l,l'- bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (0.25 g, 0.30 mmol), and potassium carbonate (0.83 g, 6.0 mmol) generally according to the procedure described for Intermediate 35 provided (±)-[5-chloro-7~(2-chlorophenyl)-2,3-dihydro-l- benzofuran-2-yl]methyl 4-methylbenzenesulfonate. Treatment of the tosylate with sodium azide (1.5 g, 23.1 mmol) generally according to the procedure described for Intermediate 98 provided (±)-2-(azidomethyl)-5-chloro-7-(2-methylphenyl)-2,3-dihydro -l-benzofuran. Treatment of the azide with sulfided platinum on carbon (120 mg, 5 wt.%) generally according to the procedure described for Example 1 gave 0.70 g (80%) of (±)-l-[5- chloro-7-(2-chlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]meth anamine as a yellow solid, hydrochloride salt, mp 231-234 °C; Anal, calcd. for CI ₅ HI ₃ CI ₂ NOHCI: C, 54.49; H,

4.27; N, 4.24. Found: C, 46.01; H, 4.17; N, 3.25.

Example 88: (±)-l-[5-chloro-7-(3-methylphenyl)-2,3-dihydro-l-benzofuran -2- yl]methanamine Treatment of (±)-2-(azidomemyl)-5-chloro-7-(3-methylphenyl)-2,3-dihydro- l- benzofuran (0.26g, 0.87 mmol) with sulfided platinum on carbon (85 mg, 5 wt.%) generally according to the procedure described for Example 1 afforded 0.14 g (59%) of (±)-l-[5-chloro-7-(3-methylphenyl)~2,3-dihydro-l -benzofuran-2-yI]methanamine as a white solid, hydrochloride salt, mp 268-271 °C; Anal, calcd. for CiβH^ClNOHCl: C, 61.95; H, 5.52; N, 4.52. Found: C, 61.01; H, 5.44; N, 4.35.

Example 89: (±)-l-[5-chloro-7-(3-chlorophenyl)-2,3-dihydro-l-benzofuran -2- yl]methanamine

Treatment of (±)-[5-chloro-7-(3-chlorophenyl)-2,3-dihydro-l -benzofuran-2- yljmethyl 4-methylbenzenesulfonate (1.00 g, 2.24 mmol) with sodium azide (0.93 g, 14.3 mmol) generally according to the procedure described for Intermediate 98 provided 0.41 g of (±)-2-(azidomethyl)-5-chloro-7-(3-chlorophenyl)-2,3-dihydro -l-benzofuran.

Treatment of the azide with sulfided platinum on carbon (100 mg, 5 wt.%) generally according to the procedure described for Example 1 provided 0.31 g (50%) of (±)-l-[5- chloro-7-(3-chlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]meth anamine as a white solid, hydrochloride salt, mp 195 °C (dec); Anal, calcd for C 15Hi ₃ Cl ₂ NOHCl: C, 54.49; H, 4.27; N, 4.24. Found: C, 51.59; H, 4.21; N, 4.02.

Example 90: (±)-(5-chloro-7-thien-3-yl-2,3-dihydro-l-benzofuran-2-yl)me thylamine

Treatment of (±)-(5-chloro-7-thien-3-yl-2,3-dihydro-l-benzofuran-2-yl)me thyl 4- methylbenzenesulfonate (0.18 g, 0.43 nimol) with sodium azide (0.11 g, 1.72 mmol) generally according to the procedure described for Intermediate 98 provided 0.13 g of (±)-2-(azidomethyl)-5 -chloro-7-thien-3 -yl-2,3 -dihydro- 1 -benzofuran. Treatment of the azide with sulfided platinum on carbon (120 mg, 5 wt.%) generally according to the procedure described for Example 1 gave 0.11 g (85%) of (±)-(5-chloro-7-thien-3-yl-2,3- dihydro-l-benzofuran-2-yl)methylamine as a light yellow solid, hydrochloride salt, mp 230 °C (dec); Anal, calcd. for C13H12CINOSHCI: C, 51.66; H, 4.34; N, 4.63. Found: C,

45.27; H, 4.19; N, 3.93.

Example 91 : (-)-(5-chloro-7-thien-3-yl-2,3-dihydro-l-benzofuran-2-yl)met hylamine

Treatment of 0.44 g of fraction 1 obtained from the chiral HPLC separation of(±)- benzyl (5-chloro-7-thien-3-yl-2,3-dihydro-l-benzofuran-2-yl)methylc arbamate

(Chiralpak AD, hexane:ethanol 1 :1) with hydrogen bromide (5 mL, 30 wt.% in acetic acid) generally according to the procedure described for Example 2 gave 0.20 g (52%) of (-)-(5-chloro-7-thien-3-yl-2,3-dihydro-l-benzofuran-2-yl)met hylamine as a white solid, hydrobromide salt, [αjp = -6.00 (c 10.0 in dimethylsulfoxide); mp 277-280 ⁰ C; Anal. calcd. for Ci ₃ H ₁₂ ClNOSHBr: C, 45.04; H, 3.78; N, 4.04. Found: C, 44.67; H, 3.64; N, 3.84.

Example 92: (+)-(5-chloro-7-thien-3-yl-2,3-dihydro-l-benzofuran-2-yl)met hylamine

Treatment of 0.40 g of fraction 2 obtained from the chiral HPLC separation of(±)- benzyl (5-chloro-7-thien-3-yl-2,3-dihydro-l-benzofuran-2-yl)methylc arbamate

(Chiralpak AD, hexane:ethanol 1 :1) with hydrogen bromide (5 mL, 30 wt.% in acetic acid) generally according to the procedure described for Example 2 gave 0.31 g (89%) of

(+)-(5-chloro-7-thien-3-yl-2,3-dihydro-l-benzofuran-2-yl)met hylamine as a white solid, hydrobromide salt. [α]n = +5.01 (c 10.0 in dimethylsulfoxide); mp 277-280 °C; Anal, calcd. for Ci ₃ H^ClNOSHBr: C, 45.04; H, 3.78; N, 4.04. Found: C, 44.88; H, 3.69; N,

3.86.

Example 93: (+)-N-[(5-chloro-7-thien-3-yl-2,3-dihydro-l-benzofuran-2-yI) methyl]- JV-methylamine

To a solution of fraction 1 obtained from the chiral HPLC separation of(±)-benzyl (5-chlorό-7-thien-3-yl-2 ₃ 3-dihydro-l-benzofuran-2-yl)methylcarbamate (0.50 g, 1.25 mmol) in tetrahydrofuran (20 niL) was added lithium aluminum hydride (0.30 g, 7.5 mmol, 95 wt.%) and the reaction mixture was allowed to stir at room temperature for 5 h. The reaction mixture was quenched with ethyl aceate (5 mL) and partitioned between tetrahydrofuran (50 mL) and water (20 mL). The organic layer was separated and washed with saturated aqueous sodium bicarbonate (50 mL) and saturated aqueous sodium chloride (50 mL), was dried (magnesium sulfate), and the solvent was removed in vacuo to provide a crude oil. Purification by flash column chromatography (silica, dichloromethane methanol 39:1) provided a light brown oil. The oil was re-dissolved in THF (50 mL), aqueous hydrogen chloride (1.0 N, 1.5 mL) was added, and the resulting precipitate was filtered and washed with diethyl ether (15 mL) to afford 0.14 g (35%) of (+)-N-[(5-chloro-7-thien-3-yl-2,3-dihydro-l-benzofuran-2-yl) methyl]-N-methylamine as a white solid, hydrochloride salt. [α]β ⁵ = +6.6 (c 10.0 in methanol); mp 263-266 °C; Anal, calcd. for C14H14CINOSHCI: C, 53.17; H, 4.78; N, 4.43. Found: C, 52.5; H, 4.88; N, 4.26.

Example 94: (-)-iV-[(5-chloro-7-thien-3-yl-2,3-dihydro-l-benzofuran-2-yl )methyl]-iV- methylamine

Treatment of fraction 2 obtained from the chiral HPLC separation of(±)-benzyl (5- chloro-7-thien-3-yl-2,3-dihydro-l-benzofuran-2-yl)methylcarb amate (0.57 g, 1.43 mmol) with lithium aluminum hydride (0.30 g, 7.5 mmol, 95 wt.%) generally according to the procedure described for Example 93 afforded 0.26 g (58%) of (-)-N-[(5-chloro-7-thien-3- yl-2,3-dihydro-l-benzofuran-2-yl)methyl]-N-methylamine as a white solid, hydrochloride

salt. [α]o = -8.2 (c 10.0 in methanol); mp 263-266 ⁰ C; Anal, calcd. for CI ₄ H ₁₄ CINOSHCI: C, 53.17; H, 4.78; N ₅ 4.43. Found: C ₅ 53.8; H ₅ 4.85; N, 4.25.

Example 95: (±)-l-[5-chloro-7-(2-methylphenyl)-2,3-dihydro-l-benzofuran -2- yl]methanamine

Treatment of (±)-(5-chloro-7-{[(trifluoromethyl)sulfonyl]oxy}-2 ₅ 3-dihydro-l- benzofuran-2-yl)methyl 4-methylbenzenesulfonate (1.37 g, 2.81 mmol) with 2- methylphenylboronic acid (0.65 g, 4.60 mmol), dichloro[l,l'- bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (0.25 g, 0.30 mmol), and potassium carbonate (0.83 g, 6.0 mmol) generally according to the procedure described for Intermediate 35 provided (±)-[5-chloro-7-(2-methylphenyl)-2,3-dihydro-l- benzofuran-2-yl]methyl 4-methylbenzenesulfonate. Treatment of the tosylate with sodium azide (1.04 g, 16.1 mmol) generally according to the procedure described for Intermediate 98 provided (±)-2-(azidomethyl)-5-chloro-7-(2-methylphenyl)-2,3-dihydro -l-benzofuran. Treatment of the azide with sulfided platinum on carbon (200 mg, 5 wt.%) generally according to the procedure described for Example 1 gave 0.70 g (80%) of (±)-l-[5- chloro-7-(2-methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]meth anamine as a light yellow solid, hydrochloric salt, mp 160-163 °C; Anal, calcd. for C 16H ₁₆ ClNOHCl: C, 61.95; H,

5.52; N ₅ 4.52. Found: C, 57.75; H ₅ 5.4; N ₅ 3.95.

Example 96: (+)-l-[5-chloro-7-(2-methylphenyl)-2,3-dihydro-l-benzofuran- 2- yl]methanamine

Treatment of (±)- 1 ~[5-chloro-7-(2-methylphenyl)-2,3~dihydro- 1 -benzofuran-2- yljmethanamine (0.65 g, 2.10 mmol) with diisopropylethylamine (0.813 g, 6.29) and benzyl chloroformate (0.71 g, 4.19 mmol) generally according to the procedure described for Intermediate 12 afforded (±)-benzyl [5-chloro-7-(2-methylphenyl)-2,3-dihydro-l- benzofuran-2-yl]methylcarbamate. Chiral HPLC separation of (±)-benzyl [5-chloro-7-(2- methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methylcarbamate. (Chiralpak AD ₅ ethanol) provided two fractions. Fraction 1 (R/ = 9.114 min ₅ (Chiralpak AD, ethanol); Fraction 2 (Rf = 11.426 rnin, (Chiralpak AD ₅ ethanol). Treatment of 0.27 g of fraction 1 obtained from the chiral HPLC separation of(±)-benzyl [5-chloro-7-(2-methylphenyl)-2,3-dihydro- l-benzofuran-2-yl]methylcarbamate (Chiralpak AD ₅ ethanol) with hydrogen bromide (5

mL, 30 wt.% in acetic acid) generally according to the procedure described for Example 2 gave 0.22 g (94%) of (+)-l-[5-chloro-7-(2-methylρhenyl)-2,3-dihydro-l-benzofuran -2- yl]methanamine as a white solid, hydrobromide salt, [α]^ ⁵ = +1.5 (c 10.0 in methanol); mp 170-172 °C; Anal, calcd. for C ₁₆ H ₁₆ ClNOHBr: C, 54.18; H, 4.83; N, 3.95. Found: C, 53.28; H, 4.77; N, 3.66.

Example 97: (-)-l-[5-chloro-7-(2-methylphenyl)-2,3-dihydro-l-benzofuran- 2- yljmethanamine

Treatment of 0.25 g of fraction 2 obtained from the chiral HPLC separation of(±)- benzyl [5-chloro-7-(2-methylphenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methylcarbamate (Chiralpak AD, ethanol) with hydrogen bromide (4 mL, 30 wt.% in acetic acid) generally according to the procedure described for Example 2 gave 0.17 g (78%) of (-)-l-[5-chloro- 7-(2-methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine as a white solid, hydrobromide salt, [α]" = -1.6 (c 10.0 in methanol); mp 170-172 °C; Anal, calcd. for C ₁₆ Hi ₆ ClNOHBr: C, 54.18; H, 4.83; N, 3.95. Found: C, 53.01; H, 4.76; N, 3.78.

Example 98: (±)-l-(4-fluoro-7-phenyl-2,3-dihydro-l-benzofuran-2-yl)meth anamine

Treatment of (±)-(4-fluoro-7-phenyl-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate (2.03 g, 5.09 mmol) with sodium azide (1.32 g, 20.38 mmol) generally according to the procedure described for Intermediate 98 provided (±)-2-

(azidomethyl)-4-fluoro-7-phenyl-2,3-dihydro-l-benzofuran. Treatment of the azide with palladium on carbon (0.137 g, 10 wt.%) generally according to the procedure described for Example 1 gave 0.610 g (43%) of (±)-l-(4-fluoro-7-phenyl-2,3-dihydro-l-benzofuran- 2-yl)methanamine as a white solid, hydrochloride salt, mp 254-257 °C; Anal, calcd. for C _{1 5} HHFNOHCI: C, 64.4; H, 5.40; N, 5.01. Found: C, 64.98; H, 5.48; N, 4.79.

Example 99: (±)-l-[4-fluoro-7-(2-methylphenyl)-2,3-dihydro-l-benzofuran -2- yljmethanamine

Treatment of (±)-[4-fluoro-7-(2-methylphenyl)-2,3-dihydro- 1 -benzofuran-2- yljmethyl 4-methylbenzenesulfonate (1.38 g, 3.35 mmol) with sodium azide (0.87 g,

13.38 mmol) generally according to the procedure described for Intermediate 98 afforded (±)-2-(azidomethyl)-4-fluoro-7-(2-methylphenyl)-2,3-dihydro -l-benzofuran. Treatment

of the azide with palladium on carbon (0.083 g, 10 wt.%) generally according to the procedure described for Example 1 provided 0.561 g (57%) of (±)-l-[4-fluoro-7-(2- methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine as a white solid, hydrochloride salt, mp 228-231 °C; Anal, calcd. for Ci6H ₁₆ FNOHCl: C ₃ 65.42; H, 5.83; N ₅ 4.77. Found: C, 66.01; H, 5.88; N, 4.51.

Example 100: (±)-l-[7-(2-chlorophenyl)-5-fluoro-2,3-dihydro-l-benzofuran -2- yl]methanamine

Treatment of (±)-[7-(2-chlorophenyl)-5-fluoro-2,3-dihydro-l-benzofur an-2- yl]methyl 4-methylbenzenesulfonate (6.65 g, 0.015 mol) with sodium azide (3.99 g, 0.061 mol) generally according to the procedure described for Intermediate 98 afforded (±)-2- (azidomethyl)-7-(2-chlorophenyl)-5-fluoro-2,3-dihydro- 1 -benzofuran. Treatment of the azide with triphenylphosphine (4.18 g, 0.16 mol) generally according to the procedure described for Example 21 provided 3.37 g (70%) of (±)-l-[7-(2-chlorophenyl)-5-fluoro- 2,3-dihydro-l-benzofuran-2-yl]methanamine as a white solid, hydrochloride salt, mp >250 °C (dec); Anal, calcd. for C15H13CIFNOHCI: C, 57.34; H, 4.49; N, 4.46. Found:

C, 57.45; H, 4.75; N, 4.22.

Example 101: (+)-l-[7-(2-chIorophenyl)-5-fluoro-2,3-dihydro-l-benzofuran- 2- yl]methanamine

Treatment of 1.22 g of fraction 1 obtained from the chiral HPLC separation of(±)- benzyl [7-(2-chlorophenyl)-5 -fluoro-2,3 -dihydro- 1 -benzofuran-2-yl]methylcarbamate (Chiralcel OJ, hexane:ethanol 1:1) with hydrogen bromide (20 mL, 30 wt.% in acetic acid) generally according to the procedure described for Example 22, afforded 0.319 (34%) of (+)-l-[7-(2-chlorophenyl)-5-fluoro-2,3-dihydro-l-benzofuran- 2- yl]methanamine as a white solid, hydrochloride salt, [α]^ ⁵ = +1.18 (c 10.0, methanol); mp 206-209 °C; Anal, calcd. for CI ₅ H ₁₃ CIFNOHCI: C, 57.34; H, 4.49; N ₃ 4.46. Found: C ₃ 57.52; H, 4.67; N ₃ 4.44.

Example 102: (-)-l-[7-(2-chlorophenyl)-5-fluoro-2,3-dihydro-l-benzofuran- 2- yljmethananiine

Treatment of 1.19 g of fraction 2 obtained from the chiral HPLC separation of(±)- benzyl [7-(2-chlorophenyl)-5-fluoro-2,3-dihydro-l-benzofuran-2-yl]m ethylcarbamate (Chiralcel OJ, hexane:ethanol 1:1) with hydrogen bromide (20 niL, 30 wt.% in acetic acid) generally according to the procedure described for Example 22 provided 0.108 (12%) of (-)-l-[7-(2-chlorophenyl)-5-fluoro-2,3-dihydro-l-benzofuran- 2-yl]methanamine as a white solid, hydrochloride salt, mp 206-209 °C; FAB HRMS calcd. for C ₁₅ HHCIFNO [M+ H] ⁺ : 278.0748. Found m/z 278.0730.

Example 103: (±)-l-(5-fluoro-7-phenyl-2,3-dihydro-l-benzofuran-2-yI)meth anamine Treatment of (±)-(5-fluoro-7-phenyl-2,3-dihydro- 1 -benzofuran-2-yl)methyl 4- methylbenzenesulfonate (1.50 g, 3.76 mmol) with sodium azide (0.979 g, 15.06 mmol) generally according to the procedure described for Intermediate 98 provided (±)-2- (azidomethyl)-5-fluoro-7-phenyl-2,3-dihydro-l-benzofuran. Treatment of the azide with palladium on carbon (0.101 g, 10 wt.%) generally according to the procedure described for Example 1 provided 0.719 g (68%) of (±)-l-(5-fluoro-7-phenyl-2,3-dihydro-l- benzofuran-2-yl)methanamine as a white solid, hydrochloride salt, mp 255-260 ⁰ C; Anal, calcd. for Ci ₅ H ₁₄ FNOHCl: C, 64.4; H, 5.4; N, 5.01. Found: C, 64.16; H, 5.54; N, 4.73.

Example 104: (±)-l-[5-fluoro-7-(2-methylphenyl)-2,3-dihydro-l-benzofuran -2- yljmethanamine

Treatment of (±)-[5-fluoro-7-(2-methylphenyl)-2,3-dihydro-l -benzofuran-2- yl]methyl 4-methylbenzenesulfonate (1.48 g, 3.59 mmol) with sodium azide (0.933 g, 14.35 mmol) generally according to the procedure described for Intermediate 98 gave (±)- 2-(azidomethyl)-5-fluoro-7-(2-methylphenyl)-2,3-dihydro- 1 -benzofuran. Treatment of the azide with palladium on carbon (0.101 g, 10 wt.%) generally according to the procedure described for Example 1 provided 0.555 g (53%) of (±)-l-[5-fluoro-7-(2-methylρhenyl)- 2,3-dihydro-l-benzofuran-2-yl]methanamine as a white solid, hydrochloride salt, mp 229- 234 °C; Anal, calcd. for C ₁₆ H ₁₆ FNOHCl-O.! H ₂ O: C, 65.02; H, 5.87; N, 4.74. Found: C,

64.99; H, 5.83; N, 4.77.

Example 105: (+)-l-[5-fluoro-7-(2-methylphenyl)-2,3-dihydro-l-benzofuran- 2- yl]methanamine

Treatment of 1.51 g of fraction 1 obtained from the chiral HPLC separation of(±)- benzyl [5-fluoro-7-(2-methylphenyl)-2 ₃ 3-dihydro-l-benzofuran-2-yl]methylcarbamate (Chiralcel OD, hexane:isopropanol 8:2) with palladium on carbon (0.151 g, 10 wt.%) generally according to the procedure described for Example 1 afforded 0.981 g (87%) of (+)-l-[5-fluoro-7-(2-methylphenyl)-2,3-dihydro-l-benzofuran- 2-yl]methanamine as a white solid, hydrochloride salt, [άffi = +12.18 (c 10.0, methanol); mp 227-230 °C; Anal, calcd. for Ci6H ₁₆ FNOHCl: C, 65.42; H, 5.83; N, 4.77. Found: C, 65.11; H, 5.78; N, 4.62.

Example 106: (^-l-IS-fluoro^-Cl-methylphenyO-ZjS-dihydro-l-benzofuran-l- yljmethanamine

Treatment of 1.65 g of fraction 2 obtained from the chiral HPLC separation of(±)- benzyl [5-fluoro-7-(2-methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]m ethylcarbamate (Chiralcel OD, hexane:isopropanol 4:1) with palladium on carbon (0.133 g, 10 wt.%) generally according to the procedure described for Example 1 provided 0.966 g (78%) of (-)-l-[5-fluoro-7-(2-methylphenyl)-2,3-dihydro-l-benzofuran- 2-yl]methanamine as a white solid, hydrochloride salt. [<X]D = -11.4 (c 10.0, methanol); mp 227-230 ⁰ C; Anal, calcd. for C ₁₆ H ₁₆ FNOHCl: C, 65.42; H, 5.83; N, 4.77. Found: C, 65.28; H, 5.78; N,

4.66.

Example 107: (±)-l-[5-fluoro-7-(2-fluorophenyl)-2,3-dihydro-l-benzofuran -2- yljmethanamine

Treatment of (±)-[5-fluoro-7-(2-fluorophenyl)-2,3-dihydro- 1 -benzofuran-2- yl]methyl 4-methylbenzenesulfonate (1.84 g, 4.42 mmol) with sodium azide (1.15 g, 17.67 mmol) generally according to the procedure described for Intermediate 98 afforded (±)-2-(azidomethyl)-5-fluoro-7-(2-fluorophenyl)-2,3-dihydro -l-benzofuran. Treatment of the azide with palladium on carbon (0.111 g, 10 wt.%) generally according to the procedure described for Example 1 provided 1.02 g (77%) of (±)-l-[5-fluoro-7-(2- methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine as a white solid, hydrochloride salt, mp 240-247 ⁰ C (dec); Anal, calcd. for C \ 5H ₁ 3F2NOHCI: C, 60.51 ;

H, 4.74; N, 4.7. Found: C, 60.33; H, 4.69; N, 4.4.

Example 108: (±)-l-{5-fluoro-7-[2-(trifluoromethyl)phenyl]-2,3-dihydro-l - benzofuran-2-yl}methanamine

Treatment of (±)-{5-fluoro-7-[2-(trifluoromethyl)phenyl]-2,3-dihydro-l - benzofuran-2-yl}methyl 4-methylbenzenesulfonate (5.34 g, 0.011 mol) with sodium azide (2.60 g, 0.04 mol) generally according to the procedure described for Intermediate 98 provided (±)-2-(azidomethyl)-5-fluoro-7-[2-(trifluoromethyl)phenyl]- 2,3-dihydro-l- benzofuran. Treatment of the azide with triphenylphosphine (2.89 g, 0.011 mol) generally according to the procedure described for Example 21 afforded 3.25 g (89%) of (±)-l-{5- fluoro-7-[2-(trifluoromethyl)phenyl]-2,3-dihydro-l-benzofura n-2-yl}methanamine as a white solid, hydrochloride salt, mp 196-198 ⁰ C (dec); Anal, calcd. for C16H13F4NOHCI:

C, 55.26; H, 4.06; N,4.03. Found: C, 55.88; H, 4.26; N, 3.77.

Example 109: (±)-(4,5-difluoro-7-phenyl-2,3-dihydro-l-benzofuran-2- yl)methylamine Treatment of (±)-(4,5-difluoro-7-phenyl-2,3-dihydro-l-benzofuran-2-yl)me thyl azide (0.60 g, 2.09 mmol) in methanol (40 mL) with sulfided platinum on carbon (0.15 g, 5 wt.%) generally according to the procedure described for Example 1 provided 0.60 g (96%) of (±)-(4,5-difluoro-7-phenyl-2,3-dihydro-l-benzofuran-2-yl)me thylamine as a pink solid, hydrochloride salt, mp >240 ⁰ C; Anal, calcd. for Ci5Hi3F2NOHCl-0.5 H2O: C, 58.74; H, 4.93; N, 4.57. Found: C, 58.6; H, 4.56; N, 4.33.

Example 110: (±)-l-[4,5-difluoro-7-(2-methylphenyl)-2,3-dihydro-l-benzof uran-2- yljmethanamine

Treatment of (±)-[4,5-difluoro-7-(2-methylphenyl)-2,3-dihydro-l -benzofuran-2- yljmethyl azide (0.85 g, 2.82 mmol) with sulfided platinum on carbon (0.30 g, 5 wt.%) generally according to the procedure described for Example 1 gave 0.78 g (67%) of (±)-l- [4,5-difluoro-7-(2-methylphenyl)-2,3-dihydro-l-benzofuran-2- yl]methanamine as a grey solid, hydrochloride salt, mp >224-227 ⁰ C; Anal, calcd. for Ci ₆ Hi ₅ F ₂ NOHCl-0.4 H ₂ O:

C, 60.25; H, 5.31; N, 4.39. Found: C, 59.98; H, 5.33; N, 4.39.

Example 111: (±)-l-(5-chloro-7-methoxy~2,3-dikydro-l-benzofuran-2- yl)methanamine

Treatment of (±)-(5-chloro-7-methoxy-2,3-dihydro-l-benzofuran-2-yl)methy l 4- methylbenzenesulfonate (1.10 g, 2.98 mmol) with sodium azide (1.5 g, 23.1 mmol) generally according to the procedure described for Intermediate 98 provided (±)-2- (azidomethyl)-5-chloro-7-methoxy-2,3-dihydro-l-benzofuran. Treatment of the azide with sulfided platinum on carbon (0.080 g, 5 wt.%) generally according to the procedure described for Example 1 afforded 0.415 g (56%) of (±)-l-(5-chloro-7-methoxy-2,3- dihydro-l-benzofuran-2-yl)methanamine as a white solid, hydrochloride salt, mp 195-198 °C; Anal, calcd. for C IQHI 2ClNO ₂ HCl: C, 48.02; H, 5.24; N, 5.6. Found: C, 46.41; H,

5.09; N, 5.31.

Example 112: (±)-l-(5-chloro-2-methyl-7-phenyl-2,3-dihydro-l-benzofuran- 2- yl)methanamine

Treatment of (±)-(5-chloro-2-methyl-7-{[(trifluoromethyl)sulfonyl]oxy}-2 ,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (5.00 g, 10.0 mmol) with phenylboronic acid (1.83 g, 15.0 mmol), dichloro[l,l'- bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (0.82 g, 1.0 mmol), and potassium carbonate (2.76 g, 20.0 mmol) generally according to the procedure described for Intermediate 35 gave (±)-(5-chloro-2-methyl-7-phenyl-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate. Treatment of (±)-(5- chloro-2-methyl-7-phenyl-2,3-dihydro- 1 -benzofuran-2-yl)methyl 4- methylbenzenesulfonate (4.1 g, 9.5 mmol) with sodium azide (3.9 g, 60.0 mmol) generally according to the procedure described for Intermediate 98 afforded (±)-2- (azidomethyl)-5 -chloro-2-methyl-7-pheny 1-2,3 -dihydro- 1 -benzofur an. Treatment of the azide with sulfided platinum on carbon (0.350 g, 5 wt.%) generally according to the procedure described for Example 1 provided 2.0 g (64%) of (±)-l-(5-chloro-2-methyl-7- phenyl-2,3-dihydro-l-benzofuran-2-yl)methanamine as a white solid, hydrochloride salt, mp 222-225 °C; Anal, calcd. for Ci 6H ₁₆ ClNOHCl: C, 61.95; H, 5.52; N, 4.52. Found: C,

60.82; H, 5.67; N, 4.37.

Example 113: (±)-(5-chIoro-2-methyl-7-thien-3-yl-2,3-dihydro-l-benzofura n-2- yl)methylamine

Treatment of (±)-(5-chloro-2-methyl-7-{ [(trifluoromethyl)sulfonyl]oxy}-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (5.00 g, 10.0 mmol), thiophene-3-boronic acid (1.92 g, 15.0 mmol), dichloro[l,l'- bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (0.82 g, 1.0 mmol), and potassium carbonate (2.76 g, 20.0 mmol) generally according to the procedure described for Intermediate 35 provided (±)-(5-chloro-2-methyl-7-thien-3-yl- 2,3-dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate. Treatment of the tosylate with sodium azide (2.00 g, 30.7 mmol) generally according to the procedure described for Intermediate 98 gave (±)-2-(azidomethyl)-5-chloro-2-methyl-7-thien-3-yl- 2,3-dihydro-l-benzofuran. Treatment of the azide with sulfided platinum on carbon

(0.250 g, 5 wt.%) generally according to the procedure described for Example 1 afforded 0.7 g (22%0 of (±)-(5-chloro-2-methyl-7-thien-3-yl-2,3-dihydro-l-benzofura n-2- yl)methylamine as a white solid, hydrochloride salt, mp 295-298 °C (dec); Anal, calcd. for CI ₄ H ₁₄ CINOSHCI: C, 53.17; H, 4.78; N; 4.43. Found: C, 52.80; H, 4.74; N, 4.24.

Example 114: (±)-(5-chloro-2-methyl-7-thien-2-yl-2,3-dihydro-l-benzofura n-2- yl)methylamine

Treatment of (±)-(5-chloro-2-methyl-7-{ [(trifluoromethyl)sulfonyl]oxy}-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (2.90 g, 5.8 mmol), thiophene-2-boronic acid (1.11 g, 8.7 mmol), dichloro[l,l'- bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (0.47 g, 0.58 mmol), and potassium carbonate (1.6 g, 11.6 mmol) generally according to the procedure described for Intermediate 35 gave (±)-(5-chloro-2-methyl-7-thien-2-yl-2,3-dihydro-l- benzofuran-2-yl)methyl 4-methylbenzenesulfonate. Treatment of the tosylate with sodium azide (2.00 g, 30.7 mmol) generally according to the procedure described for Intermediate 98 provided (±)-2-(azidomethyl)-5-chloro-2-methyl-7-thien-2-yl-2,3-dihy dro-l - benzofuran. Treatment of the azide with sulfided platinum on carbon (0.250 g, 5 wt.%) generally according to the procedure described for Example 1 afforded 0.58 g of (±)-(5- chloro-2-methyl-7-thien-2-yl-2 ₃ 3-dihydro-l-benzofuran-2-yl)methylamine as a white solid, hydrochloride salt, mp 251-252 ⁰ C; Anal, calcd. for CI ₄ HI ₄ C1NOSHC1: C, 53.17;

H, 4.78; N, 4.43. Found: C, 51.17; H, 4.48; N, 4.32.

Example 115: (-)-l-(7-terf-butyl-5-methoxy-2,3-dihydro-l-benzofuran-2- yl)methanamine

Treatment of 0.211 g of fraction 1 obtained from the chiral HPLC separation of (±)-benzyl (7-fert-butyl-5-methoxy-2,3-dihydro- 1 -benzofuran-2-yl)methylcarbamate (R^ = 4.39 min, Chiralpak OD, 2-butanol: carbon dioxide 2:8) with palladium on carbon (0.021 g, 10 wt.%) generally according to the procedure described for Example 1 gave 0.098 g (63%) of (-)-l-(7-ført-butyl-5-methoxy-2,3-dihydro-l-benzofuran-2- yl)methanamine as a white solid, hydrochloride salt, mp 157-159 ⁰ C; [α]^ ⁵ = -32.46 (c 10.0 in methanol); Anal, calcd. for C ₁₄ H ₂ INO ₂ HCl: C, 61.87; H, 8.16; N, 5.15. Found: C, 59.03; H, 7.86; N ₅ 4.77.

Example 116: (+)-l-(7-ter^butyl-5-methoxy-2,3-dihydro-l-beiizofuran-2- yl)methanamine

Treatment of 0.264 g of fraction 2 obtained from the chiral HPLC separation of (±)-benzyl [(7-tert-butyl-5-methoxy-2,3-dihydro-l-benzofuran-2-yl)methy l]carbamate (R^

= 5.07 min, Chiralpak OD, 2-butanol:carbon dioxide 2:8) with palladium on carbon (0.026 g, 10 wt.%) generally according to the procedure described for Example 1 gave 0.098 g (50%) of (+)-l-(7-tert-butyl-5-methoxy-2,3-dihydro-l-benzofuran-2- yl)methanamine as a white solid, hydrochloride salt, [α]^ ⁵ = +31.9 (c 10.0 in methanol); mp 157-159 °C; Anal, calcd. for Ci ₄ H ₂ INO ₂ HCl: C, 61.87; H, 8.16; N, 5.15. Found: C, 60.04; H, 8.09; N, 4.78.

Example 117: (±)-l-{7-[(l£)-3,3-dimethylbut-l-enyl]-2,3-dihydro-l-benzo furan-2- yl}methanamine Treatment of (±)-{7-[(l _J E)-3,3-dimethylbut-l-enyl]-2,3-dihydro-l-benzofuran-2- yl}methyl 4-methylbenzenesulfonate (6.54 g, 16.92 mmol) with sodium azide (4.37 g, 67.68 mmol) generally according to the procedure described for Intermediate 98 afforded (±)- {7- [(I E)-3 ,3 -dimethylbut- 1 -enyl] -2,3-dihydro- 1 -benzofuran-2-yl } methyl azide. Treatment of the azide (1.78 g, 6.92 mmol) with triphenylphosphine (1.81 g, 6.92 mmol) generally according to the procedure described for Example 21 afforded 0.454 g (28%) of (±)-l-{7-[(lE)-3,3-dimethylbut-l-enyl]-2,3-dihydro-l-benzof uran-2-yl}methanamine as a

white solid, hydrochloride salt, mp 216-218 ⁰ C; Anal, calcd. for C15H21NOHCI: C, 67.28; H, 8.28; N ₅ 5.23. Found: C, 66.19; H, 8.27; N, 5.14.

Example 118: (±)-l-[7-(3,3-dimethylbutyl)-2,3-dihydro-l-benzofuran-2- yljmethanamine

Treatment of (±)- { 7-[( 1 £)-3 ,3-dimethylbut- 1 -enyl] -2,3-dihydro- 1 -benzofuran-2- yl}methyl azide (1.82 g, 7.07 mmol) with palladium on carbon (0.18 g, 10 wt.%) generally according to the procedure described for Example 1 provided 0.642 g (34%) of (±)-l-[7-(3,3-dimethylbutyl)-2,3-dihydro-l-benzofuran-2-yl] methanamine as a white solid, hydrochloride salt, mp 158-160 °C; Anal, calcd. for C15H23NOHCI: C, 66.77; H, 8.97; N, 5.19. Found: C, 66.31; H, 8.56; N, 5.09.

Example 119: (±)-l-{7-[(E)-2-phenyIvinyl]-2,3-dihydro-l-benzofuran-2- yl}methanamine Treatment of (±)-{7-[(E)-2-phenylvinyl]-2,3-dihydro-l-benzofuran-2-yl}me thyl

4-methylbenzenesulfonate (6.53 g, 16.06 mmol) with sodium azide (4.17 g, 64.25 mmol) generally according to the procedure described for Intermediate 98 afforded (±)-{7-[(E)- 2-phenylvinyl]-2,3-dihydro-l-benzofuran-2-yl}methyl azide. Treatment of (±)-{7-[(ϋT)-2- phenylvinyl]-2,3-dihydro-l-benzofuran-2-yl}methyl azide (2.2 g, 7.9 mmol) with triphenylphosphine (2.08 g, 7.9 mmol) generally according to the procedure described for Example 21 afforded 0.675 g (34%) of (±)-l-{7-[(£)-2-phenylvinyl]-2,3-dihydro-l- benzofuran-2-yl}methanamme as a white solid, hydrochloride salt, mp 209-211 °C; Anal, calcd. for C ₁₇ H ₁₇ NOHCl: C, 70.95; H, 6.3; N, 4.87. Found: C, 69.63; H, 6.46; N, 4.72.

Example 120: (±)-l-[7-(2-phenylethyI)-2,3-dihydro-l-benzofuran-2-yl]meth anamine

Treatment of (±)- {7- [(£)-2-phenylvinyl] -2,3-dihydro- 1 -benzofuran-2-yl } methyl azide (2.2 g, 7.9 mmol) with palladium on carbon (0.22 g, 10 wt.%) generally according to the procedure described for Example 1 provided 1.1 g (48%) of (±)-l-[7-(2- phenylethyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine as a white solid, hydrochloride salt, mp 155-157 °C; Anal, calcd. for C ₁₇ H ₁₉ NOHCl: C, 70.46; H, 6.96; N, 4.83. Found: C, 70.11; H, 7.08; N, 4.62.

Example 121 : (±)-l-[4-(4-methylphenyl)-2,3-dihydro-l-benzofuran-2- yljmethanamine

Treatment of (±)-(4-bromo-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate (5.0 g, 13.0 mmol), o-tolylboronic acid (2.66 g, 19.57 mmol), dichlorobis(tri-o-tolylphosphine)-palladium(II) (0.512 g, 0.651 mmol), and potassium carbonate (4.51 g, 32.63 mmol) generally according to the procedure described for Intermediate 37 provided 4.0 g (77%) of (±)-l-[4-(4-methylphenyl)-2,3-dihydro-l- benzofuran-2-yl]methanamine as a yellow oil. Treatment of (±)-(4-bromo-2,3-dihydro-l- benzofuran-2-yl)methyl 4-methylbenzenesulfonate (3.8 g, 9.63 mmol) with sodium azide (2.5 g, 38.53 mmol) generally according to the procedure described for Intermediate 98 gave 2.39 g (94%) of [4-(4-methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl azide. Treatment of the azide with palladium on carbon (0.239 g, 10 wt.%) generally according to the procedure described for Example 1 provided 2.3 g (93%) of (±)-l-[4-(4- methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine as a white solid, hydrochloride salt, mp 239-241 ⁰ C; Anal, calcd. for C^HiγNOHCl: C, 69.69; H, 6.58;

N, 5.08. Found: C, 69.36; H, 6.64; N, 4.93.

Example 122: (±)-l-{4-[2-(trifluoromethyl)phenyl]-2,3-dihydro-l-benzofur an-2- yl}methanamine Treatment of (±)-(4-bromo-2,3-dihydro- 1 -benzofuran-2-yl)methyl 4- methylbenzenesulfonate (5.0 g, 13.05 mmol) with 2-(trifluoromethyl)phenylboronic acid (3.72 g, 17.57 mmol), dichlorobis(tri-o-tolylphosphine)-palladium(II) (0.512 g, 0.652 mmol), and potassium carbonate (4.5 g, 32.62 mmol) generally according to the procedure described for Intermediate 37 provided 4.5 g (77%) of (±)-{4-[2- (trifluoromethyl)phenyl] -2, 3 -dihydro- 1 -benzofuran-2-yl } methyl 4- methylbenzenesulfonate as a yellow oil. Treatment of (±)~{4-[2-(trifluoromethyl)phenyl]- 2,3-dihydro-l-benzofuran-2-yl}methyl 4-methylbenzenesulfonate (4.3 g, 9.59 mmol) with sodium azide (2.5 g, 38.46 mmol) generally according to the procedure described for Intermediate 98 gave 2.88 g (94%) of (±)-{4-[2-(trifluoromethyl)ρhenyl]-2,3-dihydro-l- benzofuran-2-yl} methyl azide. Treatment of the azide with palladium on carbon (0.28 g, 10 wt.%) generally according to the procedure described for Example 1 provided 2.46 g (83%) of (±)-l-{4-[2-(trifluoromethyl)phenyl]-2,3-dihydro-l-benzofur an-2-

yl}methanamine as a white solid, hydrochloride salt, mp 213-215 ⁰ C; Anal, calcd. for C ₁₆ H ₁₄ F ₃ NOHCl: C ₃ 58.28; H, 4.59; N, 4.25. Found: C, 58.13; H ₅ 4.65; N, 4.13.

Example 123: (-)-l-{4-[2-(trifluoromethyl)phenyl]-2,3-dihydro-l-benzofura n-2- yl}methanamine

Treatment of 0.825 g of fraction 1 obtained from the chiral HPLC separation of (±)-benzyl ({4-[2-(trifluoromethyl)phenyl]-2,3-dihydro-l-benzofuran-2- yl}methyl)carbamate (R^ = 5.701 min, Chiralcel OJ, ethanokhexane 1 :1) with palladium on carbon (0.082 g, 10 wt.%) generally according to the procedure described for Example 1 gave 0.480 g (76%) of (-)-l-{4-[2-(trifluoromethyl)phenyl]-2,3-dihydro-l-benzofura n- 2-yl}methanamine as a white solid, hydrochloride salt. [α] _D = -81.36 (c 10.0 in methanol); mp 203-206 ⁰ C; Anal, calcd. for C ₁₆ H ₁₄ F ₃ NOHCl: C, 58.28; H, 4.59; N, 4.25. Found: C, 58.12; H, 5.15; N, 3.92.

Example 124: (+)-l-{4-[2-(trifluoromethyl)phenyl]-2,3-dihydro-l-benzofura n-2- yl}methanamine

Treatment of 0.800 g of fraction 2 obtained from the chiral HPLC separation of (±)-benzyl ({4-[2-(trifluoromethyl)phenyl]-2,3-dihydro-l-benzofuran-2- yl}methyl)carbamate (R^ = 7.122 min, Chiralcel OJ, ethanol:hexane 1 :1) with palladium on carbon (0.080 g, 10 wt.%) generally according to the procedure described for Example 1 gave 0.334 g (54%) of (-)-l-{4-[2-(trifluoromethyl)phenyl]-2,3-dihydro-l-benzofura n- 2-yl}methanamine as a white solid, hydrochloride salt, [α]^ ⁵ = +79.42 (c 10.0 in methanol); mp 203-206 °C; Anal, calcd. for C ₁₆ H ₁₄ F ₃ NOHCl: C, 58.28; H, 4.59; N,

4.25. Found: C, 57.98; H, 5.36; N, 3.85.

Example 125: (±)-l-[4-(2,6-dimethylphenyI)-2,3-dihydro-l-benzofuran-2- yl] methanamine

Treatment of (±)-[4-(2,6-dimethylphenyl)-2,3-dihydro-l-benzofuran-2-yl]m ethyl 4-methylbenzenesulfonate (2.27 g, 5.55 mmol) with sodium azide (1.44 g, 22.23 mmol) generally according to the procedure described for Intermediate 98 gave 1.41 g (91%) of (±)-[4-(2,6-dimethylphenyl)-2,3-dihydro-l-benzofuran-2-yl]m ethyl azide. Treatment of

the azide with palladium on carbon (0.141 g, 10 wt.%) generally according to the procedure described for Example 1 provided 1.36 g (93%) of (±)-l-[4-(2,6- dimethylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine as a white solid, hydrochloride salt, mp 254-256 °C; Anal, calcd. for C ₁₇ Hi ₉ NOHCl: C, 70.46; H ₅ 6.96; N ₃ 4.83. Found: C, 69.03; H, 7.05; N, 4.66.

Example 126: (+)-l-[4-(2,6-dimethyIphenyl)-2,3-dihydro-l-benzofuran-2- yljmethanamine

Treatment of 0.564 g of fraction 1 obtained from the chiral HPLC separation of (±)-benzyl {[4-(2,6-dimethylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methy l}carbamate (R^ = 4.818 min, Chiralcel OD, ethanol) with palladium on carbon (0.056 g, 10 wt.%) generally according to the procedure described for Example 1 gave 0.321 g (76%) of (+)- l-[4-(2,6-dimethylphenyl)-2,3-dihydro-l-benzofuran-2-yl]meth anamine as a white solid, hydrochloride salt, [α]" = +89.54 (c 10.0 in methanol); mp >250 °C; Anal, calcd. for C17H19NOHCI: C, 70.46; H, 6.96; N, 4.83. Found: C, 68.75; H, 7.1; N, 4.32.

Example 127: (-)-l-[4-(2,6-dimethylphenyl)-2,3-dihydro-l-benzofuran-2- yl] methanamine

Treatment of 0.372 g of fraction 2 obtained from the chiral HPLC separation of (±)-benzyl {[4-(2,6-dimethylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methy l}carbamate (Rf = 6.985 min, Chiralcel OD, ethanol) with palladium on carbon (0.037 g, 10 wt.%) generally according to the procedure described for Example 1 gave 0.275 g (99%) of (-)- l-[4-(2,6-dimethylphenyl)-2,3-dihydro-l-benzofuran-2-yl]meth anamine as a white solid, hydrochloride salt, [α]^ ⁵ = -91.76 (c 10.0 in methanol); mp >250 ⁰ C; Anal, calcd. for C17H19NOHCI: C, 70.46; H, 6.96; N, 4.83. Found: C, 68.59; H ₅ 6.85; N ₅ 4.48.

Example 128: (+)-l-[7-(2-methoxyphenyl)-2,3-dihydro-l-benzofuran-2- yljmethanamine

Treatment of 0.928 g of fraction 2 obtained from the chiral HPLC separation of (±)-benzyl [7-(2-methoxyphenyl)-2 ₅ 3-dihydro- 1 -benzofuran-2-yl]methylcarbamate (Chiralcel OD, hexane:isopropanol 9:1) with palladium on carbon (0.092 g, 10 wt.%)

generally according to the procedure described for Example 1 gave 0.549 g (75%) of (+)- l-[7-(2-methoxyphenyl)-2,3-dihydro-l-benzofuran-2-yl]methana mine as a white solid, hydrochloride salt. [α]n = +9.90 (c 10.0 in methanol); mp 180-184 ⁰ C; Anal, calcd. for Ci6H ₁₇ NO ₂ HCl: C ₃ 65.86; H, 6.22; N, 4.8. Found: C, 64.46; H, 6.24; N, 4.63.

Example 129: (-)-l-[7-(2-ch!orophenyl)-2,3-dihydro-l-benzofuran-2- yl]methanamine

To a solution of (+)-benzyl {[7-(2~chlorophenyl)-2,3-dihydro-l-benzofuran-2~ yljmethyl} carbamate (0.530 g, 1.34 mmol) in acetonitrile (25 mL) cooled to 0 ⁰ C was added iodotrimethylsilane (1.07 g, 5.38 mmol) and the reaction mixture was allowed to stir for 90 min. The reaction mixture was quenched by the addition of aqueous hydrogen chloride (25 mL, 2.0 N) and washed with diethyl ether (50 mL). The aqueous layer was neutralized with aqueous sodium hydroxide (50 mL, 2.5 N) and extracted with dichloromethane (2 x 100 mL). The combined organic fractions were washed with water (75 mL), saturated aqueous sodium chloride (50 mL), dried (magnesium sulfate), and the solvent removed in vacuo to provide a crude oil. The oil was re-dissolved in isopropanol (2 mL) and hydrogen chloride (5.0 mL, 1.0 M in diethyl ether) was added. The resulting precipitate was filtered, washed (diethyl ether), and dried to afford 0.229 g (58%) of (-)-l- [7-(2-chlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamin e as a white solid, hydrochloride salt. [af _D ⁵ = -11.06 (c 10.0 in dimethylsulfoxide); mp 186-188 °C; Anal, calcd. for CI ₅ H ₁₄ CINOHCI: C, 60.83; H, 5.1; N, 4.73. Found C, 59.59; H, 5.13; N, 4.48.

Example 130: (+)-l-[7-(2-chlorophenyl)-2,3-dihydro-l-benzofuran-2- yljmethanamine Treatment of (-)-benzyl { [7-(2-chlorophenyl)-2,3-dihydro- 1 -benzofuran-2- yl]methyl} carbamate (0.480 g, 1.22 mmol) with iodotrimethylsilane (0.975 g, 4.87 mmol) generally according to the procedure described for Example 129 afforded 0.272 g (75%) of (+)-l-[7-(2-chlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]meth anamine as a white solid, hydrochloride salt, [α]" = +9.90 (c 10.0 in dimethylsulfoxide); mp 186-188 °C; Anal, calcd. for C15H14CINOHCI: C, 60.83; H, 5.1; N, 4.73. Found C, 60.53; H, 5.39; N, 4.62.

Example 131: (+)-l-[7-(3-fluorophenyl)-2,3-dihydro-l-benzofuran-2- yl] methanamine

Treatment of (+)-benzyl {[7-(3-fluorophenyl)~2,3-dihydro-l-benzofuran-2~ yljmethyl} carbamate (0.326 g, 0.864 mmol) with palladium on carbon (0.033 g, 10 wt.%) generally according to the procedure described for Example 1 provided 0.195 g (81%) of (+)-l-[7-(3-fluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]meth anamine as a white solid, hydrochloride salt. [αβ ⁵ = +18.32 (c 10.0 in methanol); mp 186-188 ⁰ C; Anal, calcd. for C ₁₅ H ₁₄ FNOHCl: C, 64.4; H, 5.4; N, 5.01. Found: C ₃ 63.32; H, 5.1; N ₅ 4.86.

Example 132: (-)~l-[7-(3-fluorophenyI)-2,3-dihydro-l-benzofuran-2- yl] methanamine

Treatment of (-)-benzyl {[7-(3-fluorophenyl)-2,3-dihydro-l-benzofuran-2- yljmethyl} carbamate (0.330 g, 0.874 mmol) with palladium on carbon (0.033 g, 10 wt.%) generally according to the procedure described for Example 1 provided 0.135 g (55%) of (-)-l-[7-(3-fluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]meth anamine as a white solid, hydrochloride salt, [α]" = -19.00 (c 10.0 in methanol); mp 186-188 ⁰ C; Anal, calcd. for C ₁₅ H ₁₄ FNOHCl: C, 64.4; H, 5.4; N, 5.01. Found: C, 63.52; H, 5.16; N, 4.91.

Example 133: (+)-l-[7-(3-methoxyphenyl)-2,3-dihydro-l-benzofuran-2- yl] methanamine

Treatment of (+)-benzyl { [7-(3-methoxyphenyl)-2,3-dihydro-l-benzofuran-2- yl]methyl}carbamate (1.36 g, 3.49 mmol) with palladium on carbon (0.136 g, 10 wt.%) generally according to the procedure described for Example 1 provided 0.70 g (79%) of (+)-l-[7-(3-methoxyphenyl)-2,3-dihydro-l-benzofuran-2-yl]met hanamine as a white solid, hydrochloride salt, [α]" = +32.44 (c 10.0 in methanol); mp 156-158 ⁰ C; Anal. calcd. for C ₁₆ H ₁₇ NO ₂ HCl: C, 65.86; H, 6.22; N, 4.8. Found: C, 65.25; H, 6.18; N, 4.69.

Example 134: (-)-l-[7-(3-methoxyphenyl)-2,3-dihydro-l-benzofuran-2- yl]methanamine Treatment of (-)-benzyl {[7-(3-methoxyphenyl)-2,3-dihydro-l-benzofuran-2- yl]methyl}carbamate (1.38 g, 3.54 mmol) with palladium on carbon (0.138 g, 10 wt.%) generally according to the procedure described for Example 1 provided 0.558 g (62%) of

(_)_l_[7-(3-methoxyphenyl)-2,3-dihydro-l-benzofuran-2-yl]met hanamine as a white solid, hydrochloride salt. [α]n = -32.14 (c 10.0 in methanol); mp 156-158 ⁰ C; Anal, calcd. for C16H17NO2HCI: C, 65.86; H, 6.22; N, 4.8. Found: C ₃ 65.03; H ₃ 6.22; N ₃ 4.7.

Example 135: (-)-l-{7-[3-(trifluoromethyl)phenyl]-2,3-dihydro-l-benzofura n-2- yl}methanamine

Treatment of 0.680 g of fraction 1 obtained from the chiral HPLC separation of (±)-benzyl ({7-[3-(trifluoromethyl)phenyl]-2,3-dihydro-l-benzofuran-2- yl}methyl)carbamate (Chiralpak OJ, isopropanol: carbon dioxide 15:85) with palladium on carbon (0.068 g, 10 wt.%) generally according to the procedure described for Example 1 gave 0.301 g (67%) of (-)-l-{7-[3-(trifluoromethyl)phenyl]-2 ₃ 3-dihydro-l-benzofuran- 2-yl}methanamine as a white solid, hydrochloride salt, [α]^ ⁵ = -31.74 (c 10.0 in methanol); mp 184-186 °C; Anal, calcd. for C16H14F3NOHCI: C, 58.28; H ₃ 4.59; N,

4.25. Found: C, 58.15; H ₃ 4.57; N ₃ 4.21.

Example 136: (+)-l-{7-[3-(trifluoromethyl)phenyl]-2,3-dihydro-l-benzofura n-2- yl}methanamine

Treatment of 0.700 g of fraction 2 obtained from the chiral HPLC separation of (±)-benzyl ({7-[3-(trifluoromethyl)phenyl]-2 ₃ 3-dihydro-l-benzofuran-2- yl}methyl)carbamate (Chiralpak OJ, isopropanol: carbon dioxide 15:85) with palladium on carbon (0.070 g, 10 wt.%) generally according to the procedure described for Example 1 gave 0.328 g (61%) of (+)-l-{7-[3-(trifluoromethyl)phenyl]-2 ₃ 3-dihydro-l-benzofuran- 2-yl}methanamine as a white solid, hydrochloride salt, [α]^, ⁵ = +31.66 (c 10.0 in methanol); mp 184-186 ⁰ C; Anal, calcd. for C ₁₆ H ₁₄ F ₃ NOHCl: C ₃ 58.28; H ₃ 4.59; N, 4.25. Found: C ₃ 57.96; H, 4.44; N ₃ 4.16.

Example 137: (+)-l-{7-[4-(trifluoromethyl)phenyl]-2,3-dihydro-l-benzofura n-2- yl}methanamine

Treatment of 0.720 g of fraction 1 obtained from the chiral HPLC separation of (±)-benzyl ({7-[4-(trifluoromethyl)phenyl]-2 ₃ 3-dihydro-l-benzofuran-2- yl}methyl)carbamate (Chiralpak AD ₃ methanol: water 95:5) with palladium on carbon

(0.072 g, 10 wt.%) generally according to the procedure described for Example 1 gave

0.411 g (74%) of (+)-l-{7-[4-(trifluoromethyl)phenyl]-2,3-dihydro-l-benzofura n-2- yl}methanamine as a white solid, hydrochloride salt. [α]p ⁵ = +15.90 (c 10.0 in methanol); mp 226-229 ⁰ C; Anal, calcd. for C16H14F3NOHCI: C ₅ 58.28; H ₅ 4.59; N ₅ 4.25. Found:

C, 57.31; H, 4.84; N ₅ 4.09.

Example 138: (-)-l-{7-[4-(trifluoromethyl)phenyl]-2,3-dihydro-l-benzofura n-2- yl}methanamine

Treatment of 0.740 g of fraction 2 obtained from the chiral HPLC separation of

(±)-benzyl ({7-[4-(trifluoromethyl)phenyl]-2 ₅ 3-dihydro-l-benzofuran-2- yl}methyl)carbamate (Chiralpak AD, methanol: water 95:5) with palladium on carbon

(0.074 g, 10 wt.%) generally according to the procedure described for Example 1 gave

0.425 g (74%) of (-)-l-{7-[4-(trifluoromethyl)phenyl]-2,3-dihydro-l-benzofura n-2- yl}methanamine as a white solid, hydrochloride salt, [α]^ ⁵ = -14.98 (c 10.0 in methanol); mp 226-229 °C; Anal, calcd. for C ₁₆ H ₁₄ F ₃ NOHCl: C ₅ 58.28; H ₅ 4.59; N, 4.25. Found: C ₅ 57.48; H ₅ 4.51; N ₅ 4.09.

Example 139: (±)-l-[7-(2,6-difluorophenyl)-2,3-dihydro-l-benzofuran~2~ yljmethanamine

Treatment of (±)-[7-(2 ₅ 6-difluorophenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methanol (3.5 g, 13.35 mmol) withj^-toluenesulfonyl chloride (3.05 g, 16.01 mol) generally according to the procedure described for Intermediate 10 gave 3.5 g (64%) of (±)-[7-(2,6- difluorophenyl)-2 ₅ 3-dihydro- 1 -benzofuran-2-yl]methyl 4-methylbenzenesulfonate. Treatment of (±)-[7-(2,6-difluorophenyl)-2 ₅ 3-dihydro-l-benzofuran-2-yl]methyl 4- methylbenzenesulfonate (3.0 g, 7.20 mmol) with sodium azide (1.87 g, 28.8 mmol) generally according to the procedure described for Intermediate 98 gave (±)-[7-(2,6- difluorophenyl)-2 ₅ 3-dihydro-l-benzofuran-2-yl]methyl azide. Treatment of the azide with palladium on carbon (0.20 g ₅ 10 wt.%) generally according to the procedure described for Example 1 provided 1.69 g (90%) of (±)-l-[7-(2 ₅ 6-difluorophenyl)-2,3-dihydro-l- benzofuran-2-yl]methanamine as a white solid, hydrochloride salt, mp 219-222 ⁰ C; Anal. calcd. for C ₁₅ H ₁₃ F ₂ NOHCl: C ₅ 60.51; H ₅ 4.74; N ₅ 4.7. Found: C ₅ 60.34; H ₅ 4.87; N, 4.58.

Example 140: (±)-l-[7-(2,6-dichIorophenyl)-2,3-dihydro-l-benzofuran-2- yljmethanamine

Treatment of (±)-[7-(2,6-dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]m ethyl 4-methylbenzenesulfonate (0.75 g, 1.67 mmol) with sodium azide (0.43 g, 6.67 mmol) generally according to the procedure described for Intermediate 98 afforded 0.48 g (90%) of (±)-[7-(2,6-dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]m ethyl azide. Treatment of the azide with triphenylphosphine (0.393 g, 1.49 mmol) generally according to the procedure described for Example 21 afforded 0.348 g (71%) of (±)-l-[7-(2,6- dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine as a white solid, hydrochloride salt, mp 206-208 ⁰ C; Anal, calcd. for C15H13CI2NOHCI: C, 54.49; H,

4.27; N ₅ 4.24. Found: C, 54.38; H ₅ 4.36; N ₅ 4.12.

Example 141: (-)-l-[7-(2,6-dichlorophenyl)-2,3-dihydro-l-benzofuran-2- yljmethanamine Treatment of 0.081 g of fraction 1 obtained from the chiral HPLC separation of

(±)-benzyl {[7-(2 ₅ 6-dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}carba mate (Chiralpak AD ₅ ethanol:hexane 1:1) with iodotrimethylsilane (0.153 g, 0.766 mmol) generally according to the procedure described for Example 129 gave 0.039 g (58%) of (- )-l-[7-(2,6-dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]me thanamine as a white solid, hydrochloride salt. [<X] _D = -29.8 (c 10.0 in dimethylsulfoxide); mp 207-209 ⁰ C; Anal, calcd. for C _{1 5} HI ₃ CI ₂ NOHCI: C ₅ 54.49; H ₅ 4.27; N ₅ 4.24. Found: C ₅ 54.74; H ₅ 3.97; N, 4.23.

Example 142: (+)-l-[7-(2,6-dichlorophenyl)-2,3-dihydro-l-benzofuran-2- yl]methanamine

Treatment of 0.132 g of fraction 2 obtained from the chiral HPLC separation of (±)-benzyl { [7-(2,6-dichlorophenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methyl} carbamate (Chiralpak AD, ethanohhexane 1:1) with iodotrimethylsilane (0.247 g, 1.23 mmol) generally according to the procedure described for Example 129 gave 0.036 g (56%) of (+)-l-[7-(2,6-dichlorophenyl)-2 ₅ 3-dihydro-l-benzofuran-2-yl]methanamine as a white solid, hydrochloride salt. [α]p = +30.0 (c 10.0 in dimethylsulfoxide); mp 207-209 °C;

Anal, calcd. for C _{1 5} HI ₃ CI ₂ NOHCI: C, 54.49; H, 4.27; N, 4.24. Found: C ₅ 54.43; H ₅ 4.017; N ₅ 4.19.

Example 143: (±)-l-[7-(2,4-dimethoxyphenyl)-2,3-dihydro-l-benzofuran-2- yl]methanamine

Treatment of (±)-[7-(2,4-dimethoxyphenyl)-2 ₅ 3-dihydro- 1 -benzofuran-2- yl]methyl 4-methylbenzenesulfonate (3.0 g ₅ 6.81 mmol) with sodium azide (1.77 g, 27.26 mmol) generally according to the procedure described for Intermediate 98 afforded (±)-2- (azidomethyl)-7-(2,4-dimethoxyphenyl)-2,3-dihydro-l-benzofur an. Treatment of the azide with palladium on carbon (0.215 g, 10 wt.%) generally according to the procedure described for Example 1 provided 1.57 g (72%) of (±)-l-[7-(2,4-dimethoxyphenyl)-2,3- dihydro-l-benzofuran-2-yl]methanamine as a white solid, hydrochloride salt, mp 175-178 ⁰ C; Anal, calcd. for C ₁₇ H ₁₉ NO ₃ HCl: C, 63.45; H ₅ 6.26; N ₅ 4.35. Found: C, 62.59; H ₅

6.25; N ₅ 4.01.

Example 144: (-)-l-[7-(2,4-dimethoxyphenyl)-2,3-dihydro-l-benzofuran-2- yljmethanamine

Treatment of (+)-benzyl {[7-(2,4-dimethoxyphenyl)-2,3-dihydro-l-benzofuran-2- yl]methyl} carbamate (0.660 g, 1.57 mmol) with palladium on carbon (0.066 g, 10 wt.%) generally according to the procedure described for Example 1 afforded 0.242 g (48%) of (-)-l-[7-(2 ₅ 4-dimethoxyphenyl)-2 ₅ 3-dihydro-l-benzofuran-2-yl]methanamine as a pale yellow solid, hydrochloride salt, [α]^ ^{5 =} -4.7 (c 10.0 in methanol); mp 166-168 ⁰ C; Anal, calcd. for C ₁₇ H ₁₉ NO ₃ HCl: C ₅ 63.45; H, 6.26; N ₅ 4.35. Found: C, 60.84; H ₅ 6.51; N ₅

3.98.

Example 145: (+)-l-[7-(2,4-dimethoxyphenyl)-2,3-dihydro-l-benzofuran-2- yljmethanamine

Treatment of (-)-benzyl { [7-(2,4-dimethoxyphenyl)-2,3-dihydro- 1 -benzofuran-2- yl]methyl} carbamate (0.638 g, 1.52 mmol) with palladium on carbon (0.066 g, 10 wt.%) generally according to the procedure described for Example 1 afforded 0.357 g (73%) of (+)-l-[7-(2,4-dimethoxyphenyl)-2 ₅ 3-dihydro-l-benzofuran-2-yl]methanamine as a pale yellow solid, hydrochloride salt, [α]" = +1.16 (c 10.0 in methanol); mp 166-168 ⁰ C;

Anal, calcd. for C17H19NO3HCI: C, 63.45; H, 6.26; N ₃ 4.35. Found: C ₅ 61.94; H, 6.85; N, 3.76.

Example 146: (±)-l-[7-(2,4-difluorophenyl)-23-dihydro-l-benzofuran-2- yl]methanamine

Treatment of (±)-[7-(2,4-difluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]m ethyl 4-methylbenzenesulfonate (4.3 g, 10.37 mmol) with sodium azide (3.03 g, 46.68 mmol) generally according to the procedure described for Intermediate 98 gave 2.91 g (98%) of (±)-[7-(2,4-difluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]m ethyl azide. Treatment of the azide with palladium on carbon (0.29 g, 10 wt.%) generally according to the procedure described for Example 1 afforded 2.3 g (76%) of (±)-l-[7-(2,4-difluorophenyl)- 2,3-dihydro-l-benzofuran-2-yl]methanamine as a white solid, hydrochloride salt, mp 222- 224 ⁰ C; Anal calcd. for Ci ₅ H ₁ SF ₂ NOHCl: C, 60.51; H, 4.74; N, 4.7. Found C, 60.65; H,

4.76; N, 4.51.

Example 147: (+)-l-[7-(2,4-difluorophenyl)-2,3-dihydro-l-benzofuran-2- yljmethanamine

Treatment of (+)-benzyl { [7-(2,4-difluorophenyl)-2,3-dihydro-l-benzofuran-2- yl] methyl} carbamate (1.1 g, 2.78 mmol) with palladium on carbon (0.135 g, 10 wt.%) generally according to the procedure described for Example 1 gave 0.312 g (43%) of (+)- l-[7-(2,4-difluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]meth anamine as a white solid, hydrochloride salt. [<X] _D = +3.58 (c 10.0 in dimethylsulfoxide); mp 222-224 ⁰ C; Anal, calcd. for Ci ₅ H ₁₃ F ₂ NOHCl: C, 60.51; H, 4.74; N, 4.7. Found: C, 59.98; H, 4.7; N, 4.64.

Example 148: (-)-l-[7-(2,4-difluorophenyl)-2,3-dihydro-l-benzofuran-2- yl] methanamine

Treatment of (-)-benzyl {[7-(2,4-difluorophenyl)-2,3-dihydro-l-benzofuran-2- yl]methyl}carbamate (0.612 g, 1.55 mmol) with palladium on carbon (0.061 g, 10 wt.%) generally according to the procedure described for Example 1 gave 0.268 g (66%) of (-)- l-[7-(2,4-difluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]meth anamine as a white solid, hydrochloride salt, [αβ ⁵ = -4.66 (c 10.0 in dimethylsulfoxide); mp 222-224 ⁰ C; Anal.

calcd. for CI ₅ HI ₃ F ₂ NOHCI: C, 60.51; H, 4.74; N, 4.7. Found: C, 60.34; H, 4.58; N, 4.48.

Example 149: (-)-l-[7-(2,4-dichlorophenyl)-2,3-dihydro-l-benzofuran-2- yl]methanamine

Treatment of (+)-benzyl {[7-(2,4-dichlorophenyl)-2,3-dihydro-l-benzofuran-2- yljmethyl} carbamate (2.06 g, 4.81 mmol) with iodotrimethylsilane (3.85g, 19.24 mmol) generally according to the procedure described for Example 129 gave 0.933g (85%) of (- )-l-[7-(2,4-dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]me thanamine as a white solid, hydrochloride salt. [α]n = -3.34 (c 10.0 in dimethylsulfoxide); mp 203-206 ⁰ C; Anal, calcd. for CI ₅ HI ₃ CI ₂ NOHCI: C, 54.59; H, 4.27; N, 4.24. Found: C, 53.69; H, 3.96; N, 3.99.

Example 150: (+)-l~[7~(2,4-dichlorophenyl)-2,3-dihydro-l-benzofuran-2- yljmethanamine

Treatment of (-)-benzyl {[7-(2,4-dichlorophenyl)-2,3-dihydro-l-benzofuran-2- yl]methyl} carbamate (1.85 g, 4.32 mmol) with iodotrimethylsilane (3.45 g, 17.28 mmol) generally according to the procedure described for Example 129 gave 1.04 g (82%) of (+)-l-[7-(2,4-dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl] methanamine as a white solid, hydrochloride salt. [α]| ⁵ = +2.7 (c 10.0 in dimethylsulfoxide); mp 201-204 ⁰ C; Anal, calcd. for C ₁₅ HI ₃ CI ₂ NOHCI: C ₅ 54.59; H, 4.27; N, 4.24. Found: C, 54.25; H, 4.12; N, 4.16.

Example 151: (-)-l-{5-fluoro-7-[2-(trifluoromethyl)phenyl]-2,3-dihydro-l- benzofuran-2-yl}methanamine

Treatment of 0.837 g of fraction 1 obtained from the chiral HPLC separation of (±)-benzyl ( { 5-fluoro-7- [2-(trifluoromethyl)phenyl] -2,3 -dihydro- 1 -benzofuran-2- yl}methyl)carbamate (R ₍ = 4.965 min, Chiralcel AD, methanol) with iodotrimethylsilane

(1.50 g, 7.51 mmol) generally according to the procedure described for Example 129 gave 0.301 g (51%) of (-)-l-{5-fluoro-7-[2-(trifluoromethyl)phenyl]-2,3-dihydro-l- benzofuran-2-yl}methanamine as a white solid, hydrochloride salt, [α]^ ⁵ = -20.00 (c 10.0

in methanol); mp 183-188 ⁰ C; Anal, calcd. for C16H13F4NOHCI: C, 55.26; H, 4.06; N, 4.03. Found: C, 53.42; H, 4.1; N, 4.4.

Example 152: (+)-l-{5-fluoro-7-[2-(trifluoromethyl)phenyl]-2,3-dihydro-l- benzofuran-2-yl}methanamine

Treatment of 0.751 g of fraction 2 obtained from the chiral HPLC separation of (±)-benzyl ({5-fluoro-7-[2-(trifluoromethyl)phenyl]-2,3-dihydro-l-benzo furan-2- yl}methyl)carbamate (R^ = 6.877 min, Chiralcel AD, methanol) with iodotrimethylsilane

(0.675 g, 3.37 mmol) generally according to the procedure described for Example 129 gave 0.211 g (36%) of (+)-l-{5-fluoro-7-[2-(trifluoromethyl)phenyl]-2,3-dihydro-l- benzofuran-2-yl}methanamine as a white solid, hydrochloride salt, [α]^ ⁵ = +18.98 (c 10.0 in methanol); mp 193-197 °C; Anal, calcd. for CI ₆ HI ₃ F ₄ NOHCI: C, 55.26; H, 4.06; N, 4.03. Found: C, 51.01; H, 3.76; N, 4.14.

Example 153: No compound.

Example 154: (±)-l-[7-(2,3-dimethylphenyl)-2,3-dihydro-l-benzofuran-2- yljmethanamine

Treatment of (±)-(7-bromo-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate (0.50 g, 1.305 mmol) with (2,3-dimethyl-phenyl)boronic acid (0.294 g, 1.96 mmol), dichlorobis(tri-o-tolylphosphine)-palladium(II) (0.041 g, 0.052 mmol), and potassium carbonate (0.41 g, 3.25 mmol) generally according to the procedure described for Intermediate 37 provided 0.335 g (62%) of (±)-[7-(2,3- dimethylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate. Treatment of (±)-[7-(2,3-dimethylphenyl)-2,3-dihydro-l-benzofuran-2-yl]m ethyl 4- methylbenzenesulfonate with sodium azide (0.134 g, 2.06 mmol) generally according to the procedure described for Intermediate 98 afforded (±)-2-(azidomethyl)-7-(2,3- dichlorophenyl)-2,3-dihydro-l-benzofuran-7 amine. To a solution of (±)-2-(azidomethyl)- 7-(2,3-dichlorophenyl)-2,3-dihydro-l-benzofuran-7 amine (0.135 g, 1.483 mmol) in tetrahydrofuran (5 mL) was added polymer supported triphenyl phosphine (0.152 g, 0.58 mmol) and the reaction mixture was allowed to stir at room temperature for 12 h. The reaction mixture was filtered (celite) and the solvent removed in vacuo to provide a

colorless oil. The oil was re-dissolved in isopropanol (3 niL) and hydrogen chloride (1.0 N in die.thyl ether, 10.0 mL) was added. The resulting precipitate was filtered, washed (diethyl ether), and dried to afford 0.075 g (54%) of (±)-l-[7-(2,3-dimethylphenyl)-2,3- dihydro-l-benzofuran-2-yl]methanamine as a white solid, hydrochloride salt, mp > 225 °C:

Example 155: (±)-{[7-(2,3-dimethoxyphenyI)-2,3-dihydro-l-benzofuran-2- yl]methyl}amine

The title compound was prepared following the general procedure of Example 154 as a light yellow solid (2.91g, 58%) from (±)-(7-bromo-2,3-dihydro-l-benzofuran-2- yl)methyl 4-methylbenzenesulfonate (6.0 g, 15.65 mmol) and (2,3- dimethoxyphenyl)boronic acid (4.27 g, 23.49 mmol). mp 219-222 °C.

Example 156: (-)-{[(7-(2,3-dimethoxyphenyl)-2,3-dihydro-l-benzofuran-2- yl]methyl}amine

Treatment of 1.46 g of fraction 1 obtained from the chiral HPLC separation of (±)- benzyl { [7-(2,3-dimethoxyphenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methyl} carbamate Chiralcel OD, 2-butanol: carbon dioxide 3:7 with palladium on carbon (0.146 g, 10 wt.%) generally according to the procedure described for Example 1 gave 0.767 g (69%) of (-)- {[(-7-(2,3-dimethoxyphenyl)-2,3-dihydro-l-benzofuran-2-yl]me thyl}amine as a tan solid, hydrochloride salt, [a]" = -65.6 (c 10.0 in methanol); mp 146-148 ⁰ C.

Example 157: (+)-{[(7-(2,3-dimethoxyphenyl)-2,3-dihydro-l-benzofuran-2- yl]methyl}amine Treatment of 1.45 g of fraction 2 obtained from the chiral HPLC separation of (±)- benzyl { [7-(2,3 -dimethoxyphenyl)-2,3 -dihydro- 1 -benzofuran-2~yl]methyl } carbamate Chiralcel OD, 2-butanol:carbon dioxide 3:7 with palladium on carbon (0.146 g, 10 wt.%) generally according to the procedure described for Example 1 gave 0.86 g (77%) of (+)- {[(7-(2,3-dimethoxyphenyl)-2,3-dihydro-l-benzofuran-2-yl]met hyl}amine as a white solid, hydrochloride salt, [α]" = +61.6 (c 10.0 in methanol); mp 146-148 °C.

Example 158: (+)-{[7-(4-chloro-2-methylphenyl)-2,3-dihydro-l-benzofuran-2 - yl] methyl} amine

Treatment of fraction 1 (0.437 g) obtained from the chiral HPLC separation of (±)-benzyl {[7-(4-chloro-2-methylphenyl)-2 ₅ 3-dihydro-l-benzofuran-2- yl] methyl} carbamate (Chiralcel AD, ethanol:hexane 1:10) in acetonitrile (25 mL) was cooled to 0 °C and treated with iodotrimethylsilane (0.883 g, 4.413 mmol) and the reaction mixture was allowed to stir at for Ih. The solvent was removed in vacuo and the residue quenched with aqueous hydrogen chloride (2.0 N) (300 mL) and washed with diethyl ether (300 mL). The aqueous layer was separated, treated with 10% potassium hydroxide and dichloromethane (600 mL). The combined organic layers were washed with water (200 mL) and saturated aqueous sodium chloride (200 mL), was dried (magnesium sulfate), and the solvent was removed in vacuo to provide 0.20 g (60%) of (+) { [-7-(4-chloro-2-methylphenyl)-2,3-dihydro- 1 -benzofuran-2-yl] methyl} amine (0.437 g, 1.07 mmol) as a white solid, hydrochloride salt. [α]p ⁵ = +10.2 (c 10.0 in methanol); mp 190-191 ⁰ C.

Example 159: (-)-{[7-(4-chloro-2-methylphenyl)-2,3-dihydro-l-benzofuran-2 - yl]methyl}amine

The title compound was prepared (0.224 g, 74%) following the general procedure of Example 158 as a white solid, hydrochloride salt from (-)-benzyl {[7-(4-chloro-2- methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}carbamate (0.40 g, 0.981 mmol) and iodotrimethylsilane (0.785 g, 3.92 mmol). [α]" = -13.0 (c 10.0 in methanol); mp 190- 191 °C.

Example 160: (±)-{[7-(2,3-difluorophenyl)-2,3-dihydro-l-benzofuran-2- yl] methyl} amine

The title compound was prepared (0.051 g, 26%) following the general procedure of Example 154 as a light yellow solid, hydrochloride salt from (±)-(7-bromo-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.50 g, 1.31 mmol) and (2,3-difluoroyphenyl)boronic acid (0.618 g, 3.91 mmol). mp 219-222 ⁰ C.

Example 161: (±)-{[7-(2,5-dimethylphenyI)-2,3-dihydro-l-benzofuran-2- yl] methyl} amine

The title compound was prepared (0.075 g, 40%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-2,3-dihydro-l- benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.50 g, 1.31 mmol) and (2,5- dimethylphenyl)boronic acid (0.618 g, 3.91 mmol). mp > 225 °C.

Example 162: (±)-{[7-(2,5-dimethoxyphenyl)-2,3-dihydro~l-benzofuran-2- yl]methyl}amine The title compound was prepared (0.043 g, 35%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-2,3-dihydro-l- benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.50 g, 1.31 mmol) and (2,5- dimethoxyphenyl)boronic acid (0.356 g, 1.96 mmol). mp 128-132 °C.

Example 163: (±)-{[7-(2,5-dichIorophenyl)-2,3-dihydro-l-benzofuran-2- yljmethyl} amine

The title compound was prepared (0.56 g, 45%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-2,3-dihydro-l- benzofuran-2-yl)methyl 4-methylbenzenesulfonate (1.43 g, 1.31 mmol) and (2,5- dichlorophenyl)boronic acid (1.07 g, 5.59 mmol). mp 203-205 °C.

Example 164: (+)-{[7-(2,5-dichlorophenyl)-2,3-dihydro-l-benzofuran-2- yl]methyl}amine

Treatment of 0.771 g of fraction 2 obtained from the chiral HPLC separation of (±)-benzyl {[7-(2,5-dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methy l}carbamate with trimethylsilyl iodide (1.44 g, 7.20 mmol) generally according to the procedure described for Example 158 gave 0.202 g (59%) of (+)-{[(7-(2,5-dichlorophenyl)-2,3- dihydro-l-benzofuran-2-yl]methyl} amine as a white solid, hydrochloride salt [α]ø ⁵ = +16.0 (c 10.0 in methanol); mp 181-183 ⁰ C.

Example 165: (-)-{[7-(2,5-dichIorophenyI)-2,3-dihydro-l-benzofuran-2- yl]methyl}amine

Treatment of 0.710 g of fraction 1 obtained from the chiral HPLC separation of (±)-benzyl {[7-(2,5-dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methy l}carbamate with trimethylsilyl iodide (1.33 g, 6.63 mmol) generally according to the procedure described for Example 158 gave 0.202 g (45%) of (-)-{[(-7-(2,5-dichlorophenyl)-2,3- dihydro-l-benzofuran-2-yl]methyl} amine as a white solid, hydrochloride salt, [α]^ ⁵ = - 14.4 (c 10.0 in methanol); mp 184-186 ⁰ C.

Example 166: (±)-{[7-(2,4,6-trichlorophenyI)-2,3-dihydro-l-benzofuran-2- yl]methyl}amine Treatment of 2,4,6-trichlorobromobenzene (14.5 g, 55.69 mmol) with 2- methoxybenzeneboronic acid (12.69 g, 83.54 mol), dichlorobis(tri-o-tolylphosphine)- palladium(II) (0.656 g, 0.835 mmol), and potassium carbonate (19.21 g, 139.22 mmol) generally according to the procedure described for Intermediate 37 provided 9.8 g (61%) of 2' 4',6'-trichloro-l,l'-biphenyl-2-yl methyl ether. To a solution of 2' 4',6'-trichloro-l,l'- biphenyl-2-yl methyl ether (9.8 g, 34.08 mmol) in dichloromethane (100 mL) cooled to - 78 °C was added boron tribromide (9.38 g, 1.0 M in dichloromethane) generally according to the procedure described for Intermediate 163 provided provided 9.2 g of 2',4',6'-trichlorobiphenyl-2-ol as a yellow solid. Treatment of 2',4',6'-trichloro-l,r- biphenyl-2-ol (9.17 g, 33.52 mmol) with potassium carbonate (18.53 g, 134.1 mmol) and allyl bromide (4.46 g, 36.87 mol), followed by refluxing the resultant allyl ether in mesitylene generally according to the procedure described for Intermediate 8 provided 3- allyl-2',4' ₃ 6'-trichloro- 1 , 1 '-biρhenyl-2-ol. Treatment of 3-allyl-2 ^l ,4',6'-trichloro- 1,1'- biphenyl-2-ol. (10.35g, 33.00 mmol) with 3-chloroperoxybenzoic acid (17.08 g, 99.00 mmol, 77%) followed by potassium carbonate (11.40 g, 82.51 mmol) generally according to the procedure described for Intermediate 9 afforded 10.4 g (95%) of (±)-[7-(2,4,6- trichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methanol. Treatment of (±)-[7-(2,4,6- trichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methanol (10.38 g, 31.49 mmol) withjo- toluenesulfonyl chloride (7.20 g, 37.79 mol) generally according to the procedure described for Intermediate 10 gave 10.5 g (68%) of (±)-[7-(2,4,6-trichlorophenyl)-2,3- dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate as a white solid. Treatment of (±)-[7-(2,4,6-trichlorophenyl)-2,3-dihydro-l-benzofuran-2-y l]methyl 4- methylbenzenesulfonate (1.38 g, 2.85 mmol) with sodium azide (0.74g, 11.4 mmol)

generally according to the procedure described for Intermediate 98 afforded 0.93 g, (92%) of (±)-2-(azidomethyl)-7-(2,4 ₅ 6-trichlorophenyl)-2,3-dihydro-l-benzofuran. To a solution of (±)-2-(azidomethyl)-7-(2,4,6-trichlorophenyl)-2,3-dihydro-l -benzofuran in tetrahydrofuran (75mL) was added polymer-supported triphenylphosphine (1.36 g, 5.24 mmol) and the reaction was allowed to stir at room temperature 12 h. The reaction mixture was filtered (celite) and the solvent removed in vacuo to provide a crude oil. Purification by flash column chromatography (silica, 10% aqueous ammonium hydroxide in methanol: ethyl acetate 1:9) provided a colorless oil. The oil was re-dissolved in isopropanol (2 mL) and hydrogen chloride (6 mL, 1.0 M in diethyl ether) was added. The resulting precipitate was filtered, washed (diethyl ether), and dried to give 0.53 g (56%) of (±)- { [7-(2,4,6-trichlorophenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methyl} amine as a white solid, hydrochloride salt, mp >225 °C.

Example 167: (±)-{[7-(4-chIoro-2-methylphenyI)-2,3-dihydro-l-benzofuran- 2- y 1] methyl} amine

The title compound was prepared (1.01 g, 13%) following the general procedure of Example 154 as a white solid, hydrochloride salt from l-bromo-4-chloro-2-methyl- benzene (5.0 g, 24.33 mmol) and (2-methoxyphenyl)boronic acid (4.8 g , 31.63 mmol). mp 175-177 °C.

Example 168: (±)-{[7-(5-chloro-2-methyIphenyl)-2,3-dihydro-l-benzofuran- 2- yl] methyl} amine

The title compound was prepared (0.68 g, 31%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-2,3-dihydro-l- benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.50 g, 1.31 mmol) and (5-chloro-2- methylphenyl)boronic acid (0.334 g, 1.96 mmol). mp 146-150 °C.

Example 169: (±)-{[7-(5-chloro-2-methoxyphenyl)-2,3-dihydro-l-benzofuran -2- yl] methyl} amine The title compound was prepared(0.68 g, 35%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-2,3-dihydro-l-

benzofuran-2-yi)rnethyl 4-methylbenzenesulfonate (0.50 g, 1.31 mmol) and (5-chloro-2- methyoxlphenyl)boronic acid (0.365 g, 1.96 mmol). mp 149-152 °C.

Example 170: (±)-[(7-pyridin-3-yl-2,3-dihydro-l-benzofuran-2-yl)methyl]a mine The title compound was prepared (0.770 g, 69%) following the general procedure of Example 154 as a light brown solid, hydrochloride salt from (±)-(7-bromo-2,3- dihydro-l-benzofuran-2-yl)rnethyl 4-methylbenzenesulfonate (4.0 g, 10.44 mmol) and pyridine-3-ylboronic acid (3.85 g, 31.31 mmol). mp 158-162 °C.

Example 171: (+)-{[7-pyridm-3-yl-2,3-dihydro-l-benzofuran-2-yl]methyl}ami ne

The title compound was prepared (0.17 g, 78%) following the general procedure of Example 129 as a yellow solid, hydrochloride salt from (+)-benzyl {[7-pyridin-3-yl- 2,3-dihydro-l-benzofuran-2-yl]methyl} carbamate (0.30 g, 0.832 mmol) and trimethylsilyl iodide (0.66g, 3.33 mmol). [αβ ⁵ = +27.2 (c 10.0 in methanol); mp 168-171 °C.

Example 172: (-)-{[7-pyridin-3-yl-2,3-dihydro-l-benzofuran-2-yl]methyl}am ine

The title compound was prepared (0.172 g, 78%) following the general procedure of Example 129 as a light yellow solid, hydrochloride salt from (+)-benzyl {[7-pyridin-3- yl-2,3-dihydro-l-benzofuran-2-yl]methyl} carbamate (0.33 g, 0.91 mmol) and trimethylsilyl iodide (0.73g, 3.64 mmol). [<X] _D = -20.4 (c 10.0 in methanol); mp 168-171 °C.

Example 173: (±)-N-[2-(aminomethyl)-2,3-dihydro-l-benzofuran-7-yl]-N- phenylamine To a solution of (±)-(7-anilino-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate (0.5 g, 1.5 mmol) in toluene (20 mL) was added bromobenzene (0.23 g, 1.5 mmol), dichloro[l,r-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (0.061 g, .075 mmol), l,l'-bis(diphenylphosphino)ferrocene (0.125 g, 0.225 mmol), and sodium tert-butoxide (0.18 g, 1.875 mmol) and the reaction mixture was allowed to reflux 3 h. The solvent was removed in vacuo. The residue was washed with water (10OmL) and ethyl acetate (5OmL). The combined organic layers were washed with saturated aqueous sodium chloride, dried (magnesium sulfate), and the

solvent removed in vacuo to provide a crude oil. Purification by flash column chromatography (silica, ethyl acetate:hexanes 3:10) afforded (±)-(7-anilino-2,3-dihydro- l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate. Treatement of (±)-(7-anilino-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate with sodium azide (0.18 g, 2.78 mmol) generally according to the procedure described for Intermediate 98 afforded (±)-2-(azidomethyl)-N-phenyl-2,3-dihydro-l-benzofuran-7-ami ne. Treatment of the azide with polymer-supported triphenylphosphine (1.09 g, 4.17 mmol) generally according to the procedure described for Example 21 provided 0.042 g, (46%) of (±)-2-(aminomethyl)- N-phenyl-2,3-dihydro-l-benzofuran-7-amine as a white solid, fumarate salt, mp 216-218 ⁰ C.

Example 174: (±)-N-[2-(aminomethyl)-2,3-dihydro-l-benzofuran-7-yl]-N-(4- methylphenyl)amine

The title compound was prepared (0.171 g, 15%) following the general procedure of Example 173 as a white solid, fumarate salt from (±)-(7-anilino-2,3-dihydro-l- benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.96g, 3.0 mmol) and 4- bromotoluene (0.51 g, 3.0 mmol). mp 226-228 ⁰ C.

Example 175: (±)-N-[2-(aminomethyl)-2,3-dihydro-l-benzofuran-7-yl]-N-(4- chlorophenyl)amine

The title compound was prepared (0.158 g, 18%) following the general procedure of Example 173 as a white solid, fumarate salt from (±)-(7-anilino-2,3-dihydro-l- benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.96g, 3.0 mol) and l-bromo-4- chlorobenzene (0.57 g, 3.0 mmol). mp 223-224 °C.

Example 176: (±)-N-[2-(aminomethyl)-2,3-dihydro-l-benzofuran-7-yl]-N-(4- methoxyphenyl)amine

The title compound was prepared (0.048 g, 5%) following the general procedure of Example 173 as a yellow solid, fumarate salt from (±)-(7-anilino-2,3-dihydro-l- benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.96g, 3.0 mmol) and l-bromo-4- methoxybenzene (0.896 g, 3.0 mmol). mp 178-180 °C.

Example 177: (±)-N-[2-(aminomethyl)-2,3-dihydro-l-benzofuran-7-yl]-N-[4- (trifluoromethyl)phenyl] amine

The title compound was prepared (0.227g, 18%) following the general procedure of Example 173 as a white solid, fumarate salt from (±)-(7-anilino-2,3-dihydro-l- benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.96g, 3.0 mmol) and l-bromo-4- (trifluoromethyl)benzene (0.675 g, 3.0 mmol). mp 218-220 °C.

Example 178: (±)-N-[2-(aminomethyl)-2,3-dihydro-l-benzofuran-7-yl]-N-(4- fluorophenyl)amme The title compound was prepared (0.066 g, 7%) following the general procedure of Example 173 as a white solid, fumarate salt from (±)-(7-anilino-2,3-dihydro-l- benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.96g, 3.0 mmol) and l-bromo-4- fluorobenzene (0.52 g, 3.0 mmol). mp 234-236 °C.

Example 179: (±)-N-[2-(aminomethyl)-2,3-dihydro-l-benzofuran-7-yl]-N-(3, 4- dichlorophenyl)amine

The title compound was prepared (0.171 g, 15%) following the general procedure of Example 173 as a white solid, fumarate salt from (±)-(7-anilino-2,3-dihydro-l- benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.96g, 3.0 mmol) and l-bromo-3,4- dichlorobenzene (0.68 g, 3.0 mmol). mp 229-231 ⁰ C.

Example 180: (±)-N-[2-(aminomethyl)-2,3-dihydro-l-benzofuran-7-yl]-N-(2, 4- dimethylphenyl)amine

The title compound was prepared (0.234 g, 24%) following the general procedure of Example 173 as a white solid, fumarate salt from (±)-(7-anilino-2,3-dihydro-l- benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.96g, 3.0 mmol) and l-bromo-2,4- dimethylbenzene (0.55 g, 3.0 mmol). mp 232-234 °C.

Example 181: (±)-N-[2-(aminomethyl)-2,3-dihydro-l-benzofuran-7-yl]-N-(3, 4- dimethylphenyl)amine

The title compound was prepared (0.115 g, 12%) following the general procedure of Example 173 as a white solid, fumarate salt from (±)-(7-anilino-2,3-dihydro-l-

benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.96g, 3.0 mmol) and l-bromo-3,4- dimethylbenzene (0.55 g, 3.0 mmol). mp 232-234 ⁰ C.

Example 182: (±)-N-[2-(aminomethyl)-2,3-dihydro-l-benzofuran-7-yl]-N-(3- methylphenyl)amine

The title compound was prepared (0.16 g, 17%) following the general procedure of Example 173 as a white solid, fumarate salt from (±)-(7-anilino-2,3-dihydro-l- benzofuran-2~yl)m ethyl 4-methylbenzenesulfonate (0.96g, 3.0 mmol) and 3- bromotoluene (0.51 g, 3.0 mmol). mp 217-218 °C.

Example 183: (±)-N-[2-(aminomethyl)-2,3-dihydro-l-benzofuran-7-yl]-N-(3- fluorophenyl)amine

The title compound was prepared (0.266 g, 28%) following the general procedure of Example 173 as a white solid, fumarate salt from (±)-(7-anilino-2,3-dihydro-l- benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.96g, 3.0 mmol) and 4-bromo-3- fluorobenzene (0.525 g, 3.0 mmol). mp 219-221 °C.

Example 184: (±)-N-2-(aminomethyl)-λ'-[3-(trifluoromethyl)phenyl]-2,3-d ihydro-l- benzofuran-7-amine The title compound was prepared (0.195 g, 18%) following the general procedure of Example 173 as a white solid, fumarate salt from (±)-(7-anilino-2,3-dihydro-l- benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.96g, 3.0 mmol) and l-bromo-3- (trifluoromethyl)benzene (0.675 g, 3.0 mmol). mp 212-214 °C.

Example 185: (±)-N-[2-(aminomethyI)-2,3-dihydro-l-benzofuran-7-yl]-N-(4- methoxy-3~methylphenyl)amine

The title compound was prepared (0.03 g, 3%) following the general procedure of Example 173 as a white solid, fumarate salt from (±)-(7-anilino-2,3-dihydro-l- benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.96g, 3.0 mmol) and 5-bromo-2- methoxytoluene (0.603 g, 3.0 mmol). mp 205-207 °C.

Example 186: (±)-N-[2-(aminomethyl)-2,3-dihydro-l-benzofuran-7-yl]-N-(3, 5- difluorophenyl)amine

The title compound was prepared (0.185 g, 19%) following the general procedure of Example 173 as a white solid, fumarate salt from (±)-(7-anilino-2,3-dihydro-l- benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.96g, 3.0 mmol) and l-bromo-3,5- difluorobenzene (0.57 g, 3.0 mmol). mp 229-231°C.

Example 187: (±)-N-[2-(aminomethyl)-2,3-dihydro-l-benzofuran-7-yl]-N-(3- trifluoromethoxy)phenyl] amine

The title compound was prepared (0.144 g, 11%) following the general procedure of Example 173 as a white solid, fumarate salt from (±)-(7-anirino-2,3-dihydro-l- benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.96g, 3.0 mmol) and l-bromo-3-

(trifluoromethoxy)benzene (0.723 g, 3.0 mmol). mp 199-201 °C.

Example 188: (±)-N-[2-(aminomethyl)-2,3-dihydro-l-benzofuran-7-yl]-N-(3- chloro-

4-methylphenyl)amine

The title compound was prepare(0.282 g, 27%) d following the general procedure of Example 173 as a white solid, fumarate salt from (±)-(7-anilino-2,3-dihydro-l- benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.96g, 3.0 mmol) and 4-bromo-2- chlorotoluene (0.63 g, 3.0 mmol). mp 225-227 ⁰ C.

Example 189: (±)-N-[2-(aminomethyI)-2,3-dihydro-l-benzofuran-7-yI]-N-(3, 5- dichlorophenyl)amine The title compound was prepared (0.065 g, 6%) following the general procedure of Example 173 as a white solid, fumarate salt from (±)-(7-anilino-2,3-dihydro-l- benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.96g, 3.0 mmol) and l-bromo-3,5- dichlorophenylbenzene (0.678 g, 3.0 mmol). mp >250 °C.

Example 190: (±)-N-[2-(aminomethyl)-2,3-dihydro-l-benzofuran-7-yl]-N-(3- chlorophenyl)amine

The title compound was prepared (0.284 g, 28%) following the general procedure of Example 173 as a white solid, fumarate salt from (±)-(7-anilino-2,3-dihydro-l- benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.96g, 3.0 mmol) and 4-bromo-3- chlorophenylbenzene (0.57 g, 3.0 mmol). mp 220-222 ⁰ C.

Example 191: (±)-N-[2-(aminomethyl)-2,3-dihydro-l-benzofuran-7-yl]-N-(4- chloro- 3-methylphenyl)amine

The title compound was prepared (0.298 g, 28%) following the general procedure of Example 173 as a white solid, fumarate salt from (±)-(7-anilino-2,3-dihydro-l- benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.96g, 3.0 mmol) and 5-bromo-3- chlorotoluene (0.629 g, 3.0 mmol). mp 225-227 ⁰ C.

Example 192: (±)-N-[2-(aminomethyl)-2,3-dihydro-l-benzofuran-7-yI]-N-(3, 5-

(limethylphenyl)amine

The title compound was prepared (0.178 g, 18%) following the general procedure of Example 173 as a white solid, fumarate salt from (±)-(7-anilino-2,3-dihydro-l- benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.96g, 3.0 mmol) and l-bromo-3,5- dimethylbenzene (0.57 g, 3.0 mmol). mp >250 °C.

Example 193: (±)-N-[2-(aminomethyl)-2,3-dihydro-l-benzofuran-7-yl]-N-(3- chloro- 4-fluorophenyl)amine The title compound was prepared (0.167 g, 16%) following the general procedure of Example 173 as a white solid, fumarate salt from (±)-(7-anilino-2,3-dihydro-l- benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.96g, 3.0 mmol) and l-bromo-3- chloro-4-fluorobenzene (0.63 g, 3.0 mmol). mp 244-245 °C.

Example 194: (±)-N-[2-(aminomethyl)-2,3-dihydro-l-benzofuran-7-yl]-N-(2- fluorophenyl)amine

The title compound was prepared(0.070g, 7%) following the general procedure of Example 173 as a white solid, fumarate salt from (±)-(7-anilino-2,3-dihydro-l- benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.96g, 3.0 mmol) and l-bromo-2- fluorobenzene (0.52 g, 3.0 mmol). mp 203-205 ⁰ C.

Example 195: (±)-{[5-fluoro-7-(2-methoxyphenyl)-2,3-dihydro-l-benzofuran -2- yl]methyl}amine

The title compound was prepared (0.16 g, 88%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-fluoro-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate 1.0 g, 2.5 mmol) and (2- methoxyphenyl)boronic acid (0.57 g, 3.7 mmol). mp 219-220 °C.

Example 196: (±)-{[5-fluoro-7-(3-fluorophenyl)-2,3-dihydro-l-benzofuran- 2- yl]methyl} amine

The title compound was prepared (0.136 g, 46%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-fluoro-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate 0.40 g, 1.0 mmol) and (3- fluorophenyl)boronic acid (0.22 g, 1.50 mmol). mp 193-194 °C.

Example 197: (±)-{[5-fluoro-7-(3-methoxyphenyl)-2,3-dihydro-l-benzofuran -2- yl]methyl}amine The title compound was prepared (0.175 g, 64%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-fluoro-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate 0.4 g, 0.996 mmol) and (3- methoxyphenyl)boronic acid (0.23 g, 1.51 mmol). mp 172-175 °C.

Example 198: (±)-{[5-fluoro-7-(3-methyIphenyl)-2,3-dihydro-l-benzofuran- 2- yl]methyl}amine

The title compound was prepared (0.178 g, 68%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-fluoro-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.4 g, 0.996 mmol) and (3- methylphenyl)boronic acid (0.21 g, 1.51 mmol). mp 228-230 °C.

Example 199: (±)-{[5-fluoro-7-(4-fluorophenyl)-2,3-dihydro-l-benzofuran- 2- yl] methyl} amine

The title compound was prepared (0.160 g, 54%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-fluoro-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.40 g, 1.0 mmol) and (4- fluorophenyl)boronic acid (0.22 g, 1.50 mmol). mp 241-243 °C.

Example 200: (±)-{[5-fluoro-7-(4-chlorophenyl)-2,3-dihydro-l-benzofuran- 2- yl]methyl}amine The title compound was prepared (0.173 g, 55%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-fluoro-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.40 g, 1.0 mmol) and (4- chlorophenyl)boronic acid (0.25 g, 1.50 mmol). mp 221-225 °C.

Example 201: (±)-{[5-fluoro-7-(4-methylphenyl)-2,3-dihydro-l-benzofuran- 2- yl]methyl}amine

The title compound was prepared (0.211 g, 72%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-fluoro-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.4 g, 0.996 mmol) and (4- methylphenyl)boronic acid (0.20 g, 1.51 mmol). mp 180-183 °C.

Example 202: (±)-{[5-fluoro-7-(4-methoxyphenyl)-2,3-dihydro-l-benzofuran -2- yl]methyl}amine

The title compound was prepared (0.209 g, 68%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-fluoro-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate 0.4 g, 0.996 mmol) and (4- methoxyphenyl)boronic acid (0.23 g, 1.51 mmol). mp 175-176 °C.

Example 203: (±)-[(5-fluoro-7-thien-3-yl-2,3-dihydro-l-benzofuran-2- yl)methyl] amine

The title compound was prepared (0.233 g, 82%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-fluoro-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.4 g, 0.996 mmol) and 3- thienylboronic acid (0.19 g, 1.51 mmol). mp 272-274 ⁰ C.

Example 204: (±)-{[5-fluoro-7-(3-furyl)-2,3-dihydro-l-benzofuran-2- yl]methyl}amine

The title compound was prepared (0.076 g, 33%) following the general procedure of Example 154 as a yellow solid, hydrochloride salt from (±)-(7-bromo-5-fiuoro-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.4 g, 0.996 mmol) and 3- furylboronic acid (0.18 g, 1.51 mmol). mp 236-239 °C.

Example 205: (±)-[(5-fluoro-7^yridin-2-yl-2,3-dmydro-l-benzofuran-2- yl)methyl] amine

The title compound was prepared (0.060 g, 11%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-fluoro-2,3- dihydro-l-benzofuran-2-yl)niethyl 4-methylbenzenesulfonate (0.60 g, 1.49 mmol) and 2-

(tri-tert-butylstannyl)pyridine (2.6 g, 7.0 mmol 85%). mp 196-198 °C.

Example 206: (±)-[(5-fluoro-7~pyridin-3~yl-2,3-dihydro-l-benzofuran-2- yl)methyl] amine The title compound was prepared (0.072 g, 13%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-fluoro-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.60 g, 1.49 mmol) and pyridin-3-ylboronic acid (0.55 g, 4.5 mmol). mp 173-175 °C.

Example 207: (-)-[(5-fluoro-7-pyridin-3-yI-2,3-dihydro-l-benzofuran-2- yl)methyl] amine

Treatment of 0.58 g of fraction 2 obtained from the chiral HPLC separation of (±)- benzyl { [7-(2,5-dichlorophenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methyl} carbamate with hydrogen bromide (6 niL, 30 wt.% in acetic acid) generally according to the procedure described for Example 2 gave 0.181 g (15%) of (-)-{[5-fluoro-7-pyridin-3-yl-2,3-dihydro- l-benzofuran-2-yl]methyl} amine as a white solid, hydrochloride salt, [α]^ ⁵ = -16.74 (c 10.0 in methanol); mp 88-90 ⁰ C.

Example 208: (+)-{[5-fluoro-7-pyridm-3-yl-2,3-dihydro-l-benzofuran-2- yl]methyl}amine

Treatment of 0.59 g of fraction 1 obtained from the chiral HPLC separation of (±)- benzyl {[7-(2,5-dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methy l}carbamate with hydrogen bromide (6 mL, 30 wt.% in acetic acid) generally according to the procedure described for Example 2 gave 0.181 g (15%) of (+)-{[5-fluoro-7-pyridin-3-yl-2,3- dihydro-l-benzofuran-2-yl]methyl}amine as a white solid, hydrochloride salt. [α]p ⁵ = +13.71 (c 10.0 in methanol); mp 86-89 ⁰ C.

Example 209: (±)-[(5~fluoro-7-pyridin-4-yl-2,3-dihydro-l-benzofuran-2- yl)methyl] amine

The title compound was prepared (0.029 g, 5%) following the general procedure of Example 154 as a off-white solid, fumarate salt from (±)-(7-bromo-5-fluoro-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.40 g, 0.996 mmol) and pyridin-4-ylboronic acid (0.18 g, 1.5 mmol). mp 170-171 °C.

Example 210: (±)-[(5-fluoro-7-pyrimidin-5-yl-2,3-dihydro-l-benzofuran-2- yl)methyl] amine

The title compound was prepared (0.010 g, 5%) following the general procedure of Example 154 as a white solid, fumarate salt from (±)-(7-bromo-5-fluoro-2,3-dihydro-l-

benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.40 g, 0.996 mmol) and pyrimidin- 5-ylboronic acid (0.52 g, 4.0 mmol). mp 65 °C (dec).

Example 211: (±)-{[7-(2,3-dichIorophenyl)-5-fluoro-2,3-dihydro-l-benzofu ran-2- yl]methyl}amine

The title compound was prepared (0.076 g, 35%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-fiuoro-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.40 g, 0.996 mmol) and 2,3-dichlorophenylboronic acid (0.856 g, 4.5 mmol). mp 185-187 °C.

Example 212: (±)-{[7-(2,3-dimethoxyphenyl)-5-fluoro-2,3-dihydro-l-benzof uran-2- yl]methyl}amine

The title compound was prepared (0.143 g, 40%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)~(7~bromo~5-fluoro-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.50 g, 1.25 mmol) and 2,3-dimethoxyphenylboronic acid (0.68 g, 3.0 mmol). mp 90-93 °C.

Example 213: (-)-{[7-(2,3-dimethoxyphenyl)-5-fluoro-2,3-dihydro-l-benzofu ran-2- yl] methyl} amine

Treatment of 0.60 g of fraction 1 obtained from the chiral HPLC separation of (±)- benzyl { [7-(2,3-dimethoxyphenyl)-2,3-dihydro-l -benzofuran-2-yl]methyl} carbamate with trimethylsilyl iodide (1.10 g, 5.6 mmol) generally according to the procedure described for Example 129 gave 0.341 g (73%) of (-)-{[7-(2,3-dimethoxyphenyl)-5- fluoro-2,3-dihydro-l-benzofuran-2-yl]methyl}amine as a white solid, hydrochloride salt. [CC] _D = -54.27 (c 10.0 in methanol); mp 173-175 °C.

Example 214: (+)-{[7-(2,3-dimethoxyphenyl)-5-fluoro-2,3-dihydro-l-benzofu ran-2- yl]methyl}amine

Treatment of 0.80 g of fraction 2 obtained from the chiral HPLC separation of (±)- benzyl {[7-(2,3-dimethoxyphenyl)-2,3-dihydro-l-benzofuran-2-yl]meth yl}carbamate with trimethylsilyl iodide (1.44 g, 7.2 mmol) generally according to the procedure described for Example 129 gave 0.253 g (41%) of (+)-{[7-(2,3-dimethoxyphenyl)-5- fluoro-2,3-dihydro-l-benzofuran-2-yl]methyl} amine as a white solid, hydrochloride salt. [α]p = +53.38 (c 10.0 in methanol); mp 166-167 ⁰ C.

Example 215: (±)-{[7-(2,4-difluorophenyl)-5-fluoro-2,3-dihydro-l-benzofu ran-2- yl]methyl}amine

The title compound was prepared (0.163 g, 52%) following the general procedure of Example 154 as a off-white solid, hydrochloride salt from (±)-(7-bromo-5-fluoro-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.40 g, 0.996 mmol) and 2,4-difluorophenylboronic acid (0.708 g, 4.5 mmol). mp 218-220 ⁰ C.

Example 216: (±)-{[7-(2,4-dichlorophenyl)-5-fluoro-2,3-dihydro-l-benzofu ran-2- yl]methyl}amme

The title compound was prepared (0.049 g, 14%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-fluoro-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.40 g, 0.996 mmol) and 2,4-dichloroρhenylboronic acid (0.856 g, 4.5 mmol). mp 107-109 °C.

Example 217: (-)-{[5-fluoro-7-(2,4-dichlorophenyl)-2,3-dihydro-l-benzofur an-2- yl]methyl}amine

Treatment of 0.50 g of fraction 1 obtained from the chiral HPLC separation of (±)- benzyl { [7-(2,4-dichloroyphenyl)-2,3 -dihydro- 1 -benzofuran-2-yl]methyl } carbamate with trimethylsilyl iodide (1.12 g, 4.40 mmol) generally according to the procedure described for Example 129 gave 0.234 g (60%) of (-)-{[5~chloro-7-(2,4-dichlorophenyl)-2,3-

dihydro-l-benzofuran-2-yl] methyl} amine as a white solid, hydrochloride salt. [α]p ⁵ = - 2.07 (c 10.0 in methanol); mp 175-178 ⁰ C.

Example 218: (+)-{[5-fluoro-7-(2,4-dichlorophenyl)-2,3-dihydro-l-benzofur an-2- yl]methyl}amine

Treatment of 0.50 g of fraction 2 obtained from the chiral HPLC separation of (±)- benzyl { [7-(2,4-dichlorophenyl)-2,3-dihydro- 1 -benzofuran-2-yl] methyl} carbamate with trimethylsilyl iodide (1.12 g, 4.40 mmol) generally according to the procedure described for Example 129 gave 0.220 g (56%) of (+)-{[5-chloro-7-(2,4-dichlorophenyl)-2,3- dihydro-l-benzofuran-2-yl] methyl}amine as a white solid, hydrochloride salt. [α]p ⁵ = +1.80 (c 10.0 in methanol); mp 203-205 °C.

Example 219: (±)-{[7-(2,4-dimethoxyphenyl)-5-fluoro-2,3-dihydro-l-benzof uran-2- yl]methyl}amine

The title compound was prepared (0.068 g, 20%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-fluoro-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.40 g, 0.996 mmol) and 2,4-dimethoxyphenylboronic acid (0.819 g, 4.5 mmol). mp 141-143 °C.

Example 220 (±)-{[7-(2,5-difluorophenyl)-5-fluoro-2,3-dihydro-l-benzofu ran-2- yl]methyl}amme

The title compound was prepared (0.068 g, 20%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-fluoro-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.40 g, 0.996 mmol) and 2,5-difluorophenylboronic acid (0.473 g, 3.0 mmol). mp 203-205 °C.

Example 221: (±)-{[7-(2,S-dichlorophenyl)-5-fluoro-2,3-dihydro-l-benzofu ran-2- yl]methyl}amine

The title compound was prepared (0.098 g, 28%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-fluoro-2,3-

dihydro-l-benzofuran-2-yl)rnethyl 4-methylbenzenesulfonate (0.40 g, 0.996 mmol) and 2,5-dichlorophenylboronic acid (0.57 g, 3.0 mmol). mp 165-166 ⁰ C.

Example 222: (±)-{[7-(2,5-dimethylphenyl)-5-fluoro-2,3-dihydro-l-benzofu ran-2- yl]methyl}amine

The title compound was prepared (0.026 g, 9%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-fluoro-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.40 g, 0.996 mmol) and 2,5-dimethylphenylboronic acid (0.45 g, 3.0 mmol). mp 153-155 °C.

Example 223: (±)-{[7-(2,5-dimethoxyphenyl)-5-fluoro-2,3-dihydro-l-benzof uran-2- yl]methyl}amine

The title compound was prepared (0.064 g, 19%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-fluoro-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.40 g, 0.996 mmol) and 2,5-dimethoxyphenylboronic acid (0.54 g, 3.0 mmol). mp 120-122 °C.

Example 224: (±)-{[5-fluoro-7-(5-methoxy-2-methylphenyl)-2,3-dihydro-l- benzofuran-2-yl] methyl} amine The title compound was prepared (0.083 g, 26%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-fluoro-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.41 g, 1.0 mmol) (5- methoxy-2-methylρhenyl)boronic acid (0.5 g, 3.0 mmol). mp 233-235 ⁰ C.

Example 225: (±)-{[5-fluoro-7-(2-methoxy-5-methylphenyl)-2,3-dihydro-l- benzofuran-2- yl]methyl}amine

The title compound was prepared (0.017 g, 5%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-fluoro-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.4Og, 1.0 mmol) (2- methoxy-5-methylphenyl)boronic acid (0.51 g, 3.0 mmol). mp 110-111 ⁰ C.

Example 226: (±)-{[7-(2,6-difluorophenyI)-5-fluoro-2,3-dihydro-l-benzofu ran-2- yl]methyl}amine

The title compound was prepared (0.140 g, 9%) following the general procedure of Example 166 as a white solid, hydrochloride salt from (2,6-difluorophenyl)boronic acid (4.0 g, 23.5 mmol) and (2-bromo-l,3-difluorobenzene (3.1 g, 15.7 mmol). mp 235- 237 ⁰ C.

Example 227: (±)-{[7-(2,6-dimethylphenyl)-5-fluoro-2,3-dihydro-l-benzofu ran-2- yl]methyl}amine The title compound was prepared (0.109 g, 3%) following the general procedure of Example 166 as a white solid, hydrochloride salt from (2,6-dimethylphenyl)boronic acid (4.0 g, 23.0 mmol) and 2-bromo-l,3-dimethylbenzene (2.9 g, 15.6 mmol). mp 241- 243 °C.

Example 228: (+)-{[7-(2,6-dimethylphenyl)-5-fluoro-2,3-dihydro-l-benzofur an-2- yl]methyl}amine

Treatment of 0.50 g of fraction 1 obtained from the chiral HPLC separation of (±)- [7-(2,6-dimethylphenyl)-5-fluoro-2,3-dihydro- 1 -benzofuran-2-yl]methyl 4- methylbenzenesulfonate with sodium azide (0.38 g, 58.5 mmol) generally according to the procedure described for Example 1 gave 0.28 g (80%) of (+)-2-(azidomethyl)-7-(2,6- dimethylphenyl)-5-fluoro-2,3-dihydro-l-benzofuran as a colorless oil. Treatment of the azide with triphenyl phosphine (0.74 g, 2.82 mmol) generally according to the procedure described for Example 154 afforded a white solid, hydrochloride salt; [α]^ ⁵ = +10.83 (c 10.0 in methanol); mp 192-194 °C.

Example 229: (-)-{[7-(2,6-dimethylphenyl)-5-fluoro-2,3-dihydro-l-benzofur an-2- yl]methyl}amine

Treatment of 0.50 g of fraction 2 obtained from the chiral HPLC separation of (±)- [7-(2,6-dimethylρhenyl)-5-fluoro-2,3-dihydro- 1 -benzofuran-2-yl] methyl 4- methylbenzenesulfonate with sodium azide (0.38 g, 58.5 mmol) generally according to

the procedure described for Example 1 gave 0.22 g (63%) of (-)-2-(azidomethyl)-7-(2,6- dimethylphenyl)-5-fluoro-2,3-dihydro-l-benzofuran as a colorless oil. Treatment of the azide with triphenyl phosphine (0.58 g, 2.22 mmol) generally according to the procedure described for Example 154 afforded a white solid, hydrochloride salt; [α]β ⁵ = -6.6 (c 10.0 in methanol); mp 180-183 °C.

Example 230: (±)-{[7-(2,6-dichlorophenyl)-5-fluoro-2,3-dihydro-l-benzofu ran-2- yl]methyl}amine

The title compound was prepared (0.21 g, 5%) following the general procedure of Example 166 as a white solid, hydrochloride salt from (5-fluoro-2- methoxyphenyl)boronic acid (3.0 g, 17.6 mmol) and 2-bromo-l,3-dichlorobenzene (2.65 g, 12.0 mmol). mp 204-205 ⁰ C.

Example 231: (±)-N-{[7-(2,6-dichlorophenyl)-5-fluoro-2,3-dihydro-l-benzo furan-2- yl]methyl}cyclopropanamine

The title compound was prepared (0.035 g, 30%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-([5-fluoro-7-(2,6- dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.14 g, 0.30 mmol) and cyclopropylamine (0.17 g, 3.0 mmol). mp 112-113 ⁰ C.

Example 232: (±)-l-cyclopropyl-N-{[7-(2,6-dichlorophenyl)-5-fluoro-2,3-d ihydro-l- benzofuran-2-yl]methyl}methanamine

The title compound was prepared (0.066 g, 54%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-([5-fluoro-7-(2,6- dichlorophenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.14 g, 0.30 mmol) and (aminomethyl)cycloρropane (0.21 g, 3.0 mmol). mp 130-133 ⁰ C.

Example 233 (±)-N-{[7-(2,6-dichlorophenyl)-5-fluoro-2,3-dihydro-l-benzo furan-2- yl]methyl}cyclobutanamine

The title compound was prepared (0.074 g, 61%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-([5-fluoro-7-(2,6- dichlorophenyl)-2,3-dihydro- 1 -benzofuran-2-yl] methyl 4-methylbenzenesulfonate (0.14 g, 0.30 mmol) and cyclobutylamine (0.21 g, 3.0 mmol). mp 128-130 ⁰ C.

Example 234: (±)-N-{[7-(2,6-dichlorophenyl)-5-fluoro-2,3-dihydro-l-benzo furan-2- yl]methyl}ethanamine

The title compound was prepared (0.068 g, 56%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-([5-fluoro-7-(2,6- dichlorophenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.15 g, 0.32 mmol) and ethylamine (0.138 g, 3.2 mmol). mp 138.140 °C.

Example 235: (±)-N-{[7-(2,6-dichlorophenyl)-5-fluoro-2,3-dihydro-l-benzo furan-2- yl]methyl}propan-l-amine The title compound was prepared (0.092 g, 84%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-([5-fluoro-7-(2,6- dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.13 g, 0.28 mmol) and propylamine (0.165 g, 2.80 mmol). mp >250 °C.

Example 236: (±)-N-{[7-(2,6-dichlorophenyl)-5-fluoro-2,3-dihydro-l-benzo furan-2- yl] methyl}propan-2-amine

The title compound was prepared (0.065 g, 66%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-([5-fluoro-7-(2,6- dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.14 g, 0.3 mmol) and isopropylamine (0.18 g, 3.0 mmol). mp 134-135 °C.

Example 237 (±)-{[7-(2,6-dichlorophenyl)-5-fluoro-2,3-dihydro-l-benzofu ran-2- yl]methyl}dimethylamine

The title compound was prepared (0.069 g, 61%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-([5-fluoro-7-(2,6- dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.14 g, 0.3 mmol) and dimethylamine (0.14 g, 3.0 mmol). mp 199-201 °C.

Example 238: (±)-l-{[7-(2,6-dichlorophenyl)-5-fluoro-2,3-dihydro-l-benzo furan-2- yl]methyl}piperidiπe

The title compound was prepared (0.074 g, 69%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-([5-fluoro-7-(2,6- dichlorophenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.12 g, 0.26 mmol) and piperidine (0.22 g, 2.6 mmol). mp 184-186 °C.

Example 239: (±)-l-{[7-(2,6-dichIorophenyl)-5-fluoro-2,3-dihydro-l-benzo furan-2- yl]methyl}morpholine The title compound was prepared (0.069 g, 61%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-([5-fluoro-7-(2,6- dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.14 g, 0.30 mmol) and morpholine (0.26 g, 3.0 mmol). mp 196-199 °C.

Example 240: (±)-l-{[7-(2,6-dichlorophenyl)-5-fluoro-2,3-dihydro-l-benzo furan-2- yl] methyl} pyrrolidine

The title compound was prepared (0.069 g, 61%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-([5-fluoro-7-(2,6- dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.13 g, 0.28 mmol) and pyrrolidine (0.20 g, 2.8 mmol). mp 65-67 ⁰ C.

Example 241: (±)-{[5-chloro-7-(2-fluorophenyl)-2,3-dihydro-l-benzofuran- 2- yl]methyl}amme

The title compound was prepared (0.017 g, 39%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-chloro-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.505 g, 1.21 mmol) and (2-fluorophenyl)boronic acid (0.6 g, 4.3 mmol). mp 235-237 °C.

Example 242: (±)-{[5-chloro-7-(2-methoxyphenyl)-2,3-dmydro-l-benzofuran- 2- yl]methyl} amine

The title compound was prepared (0.017 g, 10%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-chloro-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (1.1 g, 2.42 mmol) and (2- methoxyphenyl)boronic acid (1.55 g, 9.68 mmol). mp 240-242 °C.

Example 243: (±)-{ [5-chloro-7-(3-furyl)-2,3-dihydro-l-benzofuran-2- yl] methyl} amine The title compound was prepared (0.017 g, 9%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-chloro-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.505 g, 1.21 mmol) and 3-furylboronic acid (0.54 g, 4.82 mmol). mp >250 ⁰ C.

Example 244: (±)-{[5-chloro-7-(2,3-difluorophenyl)-2,3-dihydro-l-benzofu ran-2- yl]methyl}amine

The title compound was prepared (0.131 g, 56%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-chloro-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.505 g, 1.21 mmol) and 2,3-difiuorophenylboronic acid (0.76 g, 4.81 mmol). mp 216-218 °C.

Example 245: (-)-{[5-chloro-7-(2,3-difluorophenyl)-2,3-dihydro-l-benzofur an-2- yl]methyl}amine

Treatment of 0.66 g of fraction 1 obtained from the chiral HPLC separation of (±)~ benzyl {[5-chloro-7-(2,3-difluorophenyl)-2 _J 3-dihydro-l-benzofuran-2- yl]methyl} carbamate with hydrogen bromide (15 mL, 30 wt.% in acetic acid) generally according to the procedure described for Example 2 gave a crude salt. The salt was

washed with saturated sodium bicarbonate (200 mL) and extracted with ethyl acetate (2 x 200 mL). The combined organic layers were washed with saturated aqueous sodium chloride (100 mL), dried (sodium sulfate), and the solvent was removed in vacuo to provide a colorless oil. The oil was re-dissolved in isopropanol (3 mL) and hydrogen chloride (1.0 N in diethyl ether, 10.0 mL) was added. The resulting precipitate was filtered, washed (diethyl ether), and dried to afford 0.391 g (76%) of (-)-{[5-chloro-7- (2,3-difluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}am ine as a white solid, hydrochloride salt, [α]" = -13.8 (c 10.0 in methanol); mp 225-227 °C.

Example 246: (+)-{[5-chloro-7-(2,3-difluorophenyl)-2,3-dihydro-l-benzofur an-2- yl] methyl} amine

Treatment of 0.63 g of fraction 2 obtained from the chiral HPLC separation of (±)- benzyl { [5-chloro-7-(2,3-difluorophenyl)-2,3-dihydro- 1 -benzofuran-2- yl]methyl} carbamate with hydrogen bromide (15 mL, 30 wt.% in acetic acid) generally according to the procedure described for Example 245 gave 0.387 g (66%) of (+)-{[5- chloro-7-(2,3-difluorophenyl)-2,3-dihydro-l-benzofuran-2-yl] methyl}amine as a white solid, hydrochloride salt, [α]" = +10.6 (c 10.0 in methanol); mp 225-227 ⁰ C.

Example 247: (±)-{[5-chloro-7-(2,3-dichlorophenyl)-2,3-dihydro-l-benzofu ran-2- yl]methyl}amine

The title compound was prepared (0.160 g, 55%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-chloro-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.505 g, 1.21 mmol) and 2,3-dichlorophenylboronic acid (0.92 g, 4.81 mmol). mp 245-246 °C.

Example 248: (±)-{[5-chloro-7-(2,3-dimethylphenyl)-2,3-dihydro-l-benzofu ran-2- yl] methyl} amine

The title compound was prepared (0.072 g, 31%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-chloro-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.505 g, 1.21 mmol) and 2,3-dimethylphenylboronic acid (0.70 g, 4.81 mmol). mp 223-225 ⁰ C.

Example 249: (±)-{[5-chloro-7-(2,3-dimethoxyphenyI)-2,3-dihydro-l-benzof uran-2- y 1] m ethyl} amine

The title compound was prepared (0.137 g, 47%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-chloro-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.505 g, 1.21 mmol) and 2,3-dimethoxyphenylboronic acid (0.88 g, 4.81 mmol). mp 120-122 °C.

Example 250: (±)-{[5-chloro-7-(2,4-difluorophenyl)-2,3-dihydro-l-benzofu ran-2- yl]methyl}amine The title compound was prepared (0.134 g, 57%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-chloro-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.505 g, 1.21 mmol) and 2,4-difluorophenylboronic acid (0.76 g, 4.81 mmol). mp 216-218 °C.

Example 251: (±)-{[5-chloro-7-(2,4-dichlorophenyl)-2,3-dihydro-l-benzofu ran-2- yl]methyl}amine

The title compound was prepared (0.10 g, 42%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-chloro-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.505 g, 1.21 mmol) and 2,4-dichlorophenylboronic acid (0.92 g, 4.81 mmol). mp 202-204 °C.

Example 252: (-)-{[5-chloro-7-(2,4-dichlorophenyl)-2,3-dihydro-l-benzofur an-2- yl]methyl}amine

Treatment of 0.67 g of fraction 1 obtained from the chiral HPLC separation of (±)- benzyl { [5-chloro-7-(2,4-dichlorophenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methyl} carbamate with hydrogen bromide (15 mL, 30 wt.% in acetic acid) generally according to the procedure described for Example 245_gave 0.465 g (88%) of (-)-{[5-chloro-7-(2,4- dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl} amine as a white solid, hydrochloride salt. [α]n = -8.5 (c 10.0 in methanol); mp 237-239 ⁰ C.

Example 253: (+)-{[5-chIoro-7-(2,4-dichlorophenyI)-2,3-dihydro-l-benzofur an-2- yl] methyl} amine

Treatment of 0.42 g of fraction 2 obtained from the chiral HPLC separation of (±)- benzyl { [5-chloro-7-(2,4-dichlorophenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methyl} carbamate with hydrogen bromide (15 niL, 30 wt.% in acetic acid) generally according to the procedure described for Example 245 gave 0.275 g (83%) of (+)-{[5-chloro-7-(2,4- dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl} amine as a white solid, hydrochloride salt; [α]p = +10.1 (c 10.0 in methanol); mp 240-242 °C.

Example 254: (±)-{[5-chloro-7-(2,4-dimethoxyphenyl)-2,3-dihydro-l-benzof uran-2- yl] methyl} amine The title compound was prepared (0.075 g, 45%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-chloro-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.505 g, 1.21 mmol) and 2,4-dimethoxyphenylboronic acid (0.88 g, 4.81 mmol). mp 220-222 °C.

Example 255: (±)-{[5-chloro-7-(2,5-difluorophenyl)-2,3-dihydro-l-benzofu ran-2- yl] methyl} amine

The title compound was prepared (0.118 g, 42%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-chloro-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.505 g, 1.21 mmol) and 2,5-difluorophenylboronic acid (0.76 g, 4.81 mmol). mp 242-244 °C.

Example 256: (±)-{[5-chloro-7-(2,5-dichlorophenyl)-2,3-dihydro-l-benzofu ran-2- yljmethyl} amine

The title compound was prepared (0.137 g, 52%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-chloro-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.505 g, 1.21 mmol) and 2,5-dichlorophenylboronic acid (0.92 g, 4.81 mmol). mp 160-162 °C.

Example 257: (±)-{[5-chloro-7-(5-chloro-2-methoxyphenyI)-2,3-dihydro-l- benzofuran-2- yl]methyl}amine

The title compound was prepared (0.159 g, 56%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-chloro-2,3-

dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.505 g, 1.21 mmol) and (5-chloro-2-methoxyphenyl)boronic acid (0.90 g, 4.81 mmol). mp 174-176 ⁰ C.

Example 258: (±)-{[5-chloro-7-(3,4-difluorophenyl)-2,3-dihydro-l-benzofu ran-2- yl]methyl}amine

The title compound was prepared (0.121 g, 44%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-chloro-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.505 g, 1.21 mmol) and

3,4-difluorophenylboronic acid (0.76 g, 4.81 mmol). mp >250 °C.

Example 259 (±)-{[5-chloro-7-(3-chloro-4-fluorophenyl)-2,3-dihydro-l-be nzofuran-

2-yl]methyl}amine

The title compound was prepared (0.068 g, 47%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-chloro-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.505 g, 1.21 mmol) and

3-chloro-4-fluorophenylboronic acid (0.84 g, 4.81 mmol). mp 214-243 ⁰ C.

Example 260: (±)-{[5-chloro-7-(2,6-dimethylphenyl)-2,3-dihydro-l-benzofu ran-2- yl]methyl}amine The title compound was prepared (0.246 g, 53%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-chloro-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.505 g, 1.21 mmol) and 2,6-dimethylphenylboronic acid (2.8 g, 18.66 mmol). mp 173-175 ⁰ C.

Example 261: (-)-{[5-chloro-7-(2,6-dimethylphenyl)-2,3-dihydro-l-benzofur an-2- yl]methyl}amine

Treatment of 0.67 g of fraction 1 obtained from the chiral HPLC separation of (±)- benzyl {[5-chloro-7-(2,6-dimethylphenyl)-2,3-dihydro-l-benzofuran-2 - yl]methyl} carbamate with hydrogen bromide (15 mL, 30 wt.% in acetic acid) generally according to the procedure described for Example 245 provided 0.226 g (44%) of (-)-{[5- chloro-7-(2,6-dimethylphenyl)-2,3-dihydro-l-benzofuran-2-yl] methyl}amine as a white solid, hydrochloride salt, [α]" = -16.9 (c 10.0 in methanol); mp 200-202 °C.

Example 262: (+)-{[5-chloro-7-(2,6-dimethylphenyl)-2,3-dihydro-l-benzofur an-2- yl] methyl} amin e

Treatment of 0.66 g of fraction 2 obtained from the chiral HPLC separation of (±)- benzyl { [5-chloro-7-(2,6-dimethylphenyl)-2,3-dihydro- 1 -benzofuran-2- yl] methyl} carbamate with hydrogen bromide (15 mL, 30 wt.% in acetic acid) generally according to the procedure described for Example 245 afforded 0.339 g (67%) of (+)-{[5- chloro-7-(2,6-dimethylphenyl)-2,3-dihydro-l-benzofuran-2-yl] methyI}amine as a white solid, hydrochloride salt, [α]" = +14.9 (c 10.0 in methanol); mp 204-206 ⁰ C.

Example 263: (±)-{[5-chloro-7-(2,6-dichlorophenyl)-2,3-dihydro-l-benzofu ran-2- yl]methyl}amine

The title compound was prepared (0.072 g, 8%) following the general procedure of Example 166 as a white solid, hydrochloride salt from (5-chloro-2- methoxyphenyl)boronic acid (5.0 g, 26.88 mmol) and 2-bromo-l,3-dichlorobenzene (12.14 g, 53.76 mmol). mp 234-236 ⁰ C.

Example 264: (+)-{[5-chloro-7-(2,6-dichlorophenyl)-2,3-dihydro-l-benzofur an-2- y 1] methyl} amine Treatment of 0.80 g of fraction 2 obtained from the chiral HPLC separation of (±)- benzyl {[5-chloro-7-(2,6-dichlorophenyl)-2,3-dihydro-l-benzofuran-2 - yl]methyl}carbamate with trimethylsilyl iodide (1.46g, 7.20 mmol) generally according to the procedure described for Example 158 afforded 0.341 g (56%) of (+)-{[5-chloro-7- (2,6-dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl} amine as a white solid, hydrochloride salt, [α]" = +33.61 (c 10.0 in methanol); mp >250 ⁰ C.

Example 265: (-)-{[5-chloro-7-(2,6-dichlorophenyl)-2,3-dihydro-l-benzofur an-2- yl] methyl} amine

Treatment of 0.60 g of fraction 1 obtained from the chiral HPLC separation of (±)- benzyl-{[5-chloro-7-(2,6-dichlorophenyl)-2,3-dihydro-l-benzo furan-2- yl]methyl}carbamate with trimethylsilyl iodide (1.09 g, 5.60 mmol) generally according to the procedure described for Example 158 gave 0.253 g (55%) of (-)-{[5-chloro-7-(2,6-

dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}amin e as a white solid, hydrochloride salt. [<X]D = -31.76 (c 10.0 in methanol); mp >250 °C.

Example 266: (±)-{[(5-chIoro-7-pyridin~3-yl-2,3-dihydro~l-benzofuran-2- yl)methyl] amine

The title compound was prepared (0.162 g, 45%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-chloro-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.50 g, 1.20 mmol) and pyridin-3-ylboronic acid (0.50 g, 3.86 mmol). mp >250 °C.

Example 267: (±)-N-{[5-chloro-7-(2,6-dimethylphenyl)-2,3-dihydro-l-benzo furan-2- yl]methyl}cyclopropanamine

The title compound was prepared (0.056 g, 34%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-([5-chloro-7-(2,6- dimethylphenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.15 g, 0.338 mmol) and cyclopropylamine (0.39 g, 6.77 mmol). mp 214-216 ⁰ C.

Example 268: (±)-N-{[5-chloro-7-(2,6-dimethylphenyl)-2,3-dihydro-l-benzo furan-2- yl]methyl}(cyclopropylmethyl)amine The title compound was prepared (0.058 g, 45%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-([5-chloro-7-(2,6- dimethylρhenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.15 g, 0.338 mmol) and (aminomethyl)cycloρroρane (0.50 g, 6.77 mmol). mp 203-205 ⁰ C.

Example 269: (±)-N-{[5-chloro-7-(2,6-dimethyIphenyl)-2,3-dihydro-l-benzo furan-2- yl]methyl}cyclobutanamine

The title compound was prepared (0.027 g, 21%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-([5-chloro-7-(2,6- dimethylphenyl)-2,3-dihydro-l -benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.15 g, 0.338 mmol) and cyclobutylamine (0.49 g, 6.77 mmol). mp 203-205 °C.

Example 270: No compound

Example 271: (±)-N-{[5-chIoro-7-(2,6-dimethylphenyl)-2,3-dihydro-l-benzo furan-2- yl]methyl}ethanamine

The title compound was prepared (0.079 g, 66%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-([5-chloro-7-(2,6- dimethylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.15 g, 0.338 mmol) and ethylamine (0.14 g, 3.38 mmol). mp 230-232 °C.

Example 272: (±)-N-{[5-chIoro-7-(2,6-dimethyIphenyl)-2,3-dihydro-l-benzo furan-2- yl]methyl}propan-2-amine

The title compound was prepared (0.064 g, 52%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-([5-chloro-7~(2,6- dimethylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.15 g, 0.338 mmol) and isopropylamine (0.40 g, 6.76 mmol). mp 213-215 °C.

Example 273: No compound.

Example 274: (±)-{[5-chloro-7-(2,6-dimethylphenyl)-2,3-dihydro-l-benzofu ran-2- yl]methyl}dimethylamine The title compound was prepared (0.068 g, 57%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)~([5-chloro-7-(2,6- dimethylphenyl)-2,3 -dihydro- 1 -benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.15 g, 0.338 mmol) and dimethylamine (0.18 g, 6.76 mmol). mp 220-222 ⁰ C.

Example 275: (±)-l-{[5-chloro-7-(2,6-dimethylphenyl)-2,3-dihydro-l-benzo furan-2- yl] methy 1} piperidine

The title compound was prepared (0.095 g, 72%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-([5-chloro~7-(2,6- dimethylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.15 g, 0.338 mmol) and piperidine (0.58 g, 6.76 mmol). mp > 235 °C.

Example 276: (±)-4-{[5-chloro-7-(2,6-dimethylphenyI)-2,3-dihydro-l-benzo furan-2- yl]methyl}morpholine

The title compound was prepared (0.09 g, 68%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-([5-chloro-7-(2,6- dimethylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.15 g, 0.338 mmol) and morpholine (0.58 g, 6.76 mmol). mp 228-230 °C.

Example 277: (±)-4-{[5-chloro-7-(2,6-dimethylphenyl)-2,3-dihydro-l-benzo furan-2- yl] methyl} thiomorpholine The title compound was prepared (0.55 g, 39%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-([5-chloro-7-(2,6- dimethylphenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.15 g, 0.338 mmol) and thiomorpholine (0.72 g, 6.76 mmol). mp 224-226 °C.

Example 278: (±)-N-{[5-chloro-7-(2,6-dimethylphenyl)-2,3-dihydro-l-benzo furan-2- yl]methyl}propan-l-amine

The title compound was prepared (0.094 g, 76%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-([5-chloro-7-(2,6- dimethylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.15 g, 0.338 mmol) and propylamine (0.40 g, 6.76 mmol) mp 200-202 °C.

Example 279: (±)-l-{[5-chloro-7-(2,6-dimethylphenyl)-2,3-dihydro-l-benzo furan-2- yl]methyl}piperazine

The title compound was prepared (0.118 g, 81%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-([5-chloro-7-(2,6- dimethylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.15 g, 0.338 mmol) and piperazine (0.58 g, 6.76 mmol). mp 190-192 °C.

Example 280: (±)-l-{[5-chloro-7-(2,6-dimethylphenyl)-2,3-dihydro-l-benzo furan-2- yl]methyl}pyrrolidine

The title compound was prepared (0.094 g, 73%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-([5-chloro-7-(2,6~

dimethylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.15 g, 0.338 mmol) and pyrrolidine (0.48 g, 6.76 mmol). mp 245-247 °C.

Example 281: (±)-{[(5-methyI-7-phenyl-2,3-dihydro-l-benzofuran-2- yl)methyl] amine

Treatment of 2-bromo-4-methylphenol (19.09 g, 102 mmol) with potassium carbonate (56.0 g, 400 mmol) and allyl bromide (15.96 g, 130 mmol), followed by refluxing the resultant allyl ether in mesitylene generally according to the procedure described for Intermediate 8 provided 2-allyl-6-bromo-4-methylphenol. Treatment of 2- allyl-6-bromo-4-methylphenol (5.21 g, 23.0 mmol) with 3-chloroperoxybenzoic acid

(9.13 g, 34.50 mmol, 77%) followed by potassium carbonate (7.9 g, 57.5 mmol) generally according to the procedure described for Intermediate 9 afforded 2.14 g (43%) of (±)-(7- bromo-5-methyl-2,3-dihydro-l-benzofuran-2-yl)methanol. Treatment of (±)-(7-bromo-5- methyl-2,3-dihydro-l-benzofuran-2-yl)methanol (2.41 g, 10.0 mmol) with/?- toluenesulfonyl chloride (2.1 g, 11.0 mol) generally according to the procedure described for Intermediate 10 gave 3.31 g (84%) of (±)-(7-bromo-5-methyl-2,3-dihydro-l- benzofuran-2-yl)methyl 4-methylbenzenesulfonate as a yellow oil. Treatment of (±)-(7- bromo-5-methyl-2,3-dihydro-l -benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.25 g, 0.63 mmol) and phenylboronic acid (0.23 g, 1.89 mmol) generally according to the procedure described for Intermediate 154 afforded 0.23 g, (93%) of (±)-(5-methyl-7- phenyl-2,3-dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate. Treatment of the tosylate with sodium azide (0.19 g, 3.0 mmol) generally according to the procedure described for Intermediate 98 afforded 0.15g (97%) of (±)~2-(azidomethyl)-5-methyl-7- phenyl-2,3-dihydro- 1 -benzofuran. Treatment of (±)-2-(azidomethyl)-5-methyl-7-phenyl- 2,3-dihydro- 1 -benzofuran with polymer-supported triphenylphosphine (0.297 g, 1.13 mmol) according to the procedure described in Example 21 afforded 0.106 g (61%) of (±)-[(5-methyl-7-phenyl-2,3-dihydro-l-benzofuran-2-yl)methy l]amine as a white solid, hydrochloride salt, mp 227-228 °C.

Example 282: (±)-{[7-(2-methylphenyl)-5-methyl-2,3-dihydro-l-benzofuran- 2- yl] methyl} amine

The title compound was prepared (0.111 g, 49%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-methyl-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.30 g, 0.76 mmol) and 2- methylphenylboronic acid (0.32 g, 3.00 mmol). mp 260-263 °C.

Example 283: (±)-{[7-(2-fluorophenyl)-5-methyI-2,3-dihydro-l-benzofuran- 2- yl]methyl}amine

The title compound was prepared (0.136 g, 46%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-methyl-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.40 g, 1.00 mmol) and 2- fiuorophenylboronic acid (0.42 g, 3.00 mmol). mp 232-234 °C.

Example 284: (±)-{[7-(2-methoxyphenyl)-5-methyI-2,3-dihydro-l-benzofuran -2- yl]methyl}amine

The title compound was prepared (0.136 g, 44%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-methyl-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.40 g, 1.00 mmol) and 2- methoxyphenylboronic acid (0.46 g, 3.00 mmol). mp 194-195 ⁰ C.

Example 285: No compound.

Example 286: (±)-{[7-(2-chlorophenyl)-5-methyl-2,3-dihydro-l-benzofuran- 2- yl]methyl}amine

The title compound was prepared (0.135 g, 58%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-methyl-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.30 g, 0.76 mmol) and 2- chlorophenylboronic acid (0.35 g, 2.28 mmol). mp 260-263 ⁰ C.

Example 287: (±)-({5-methyI-7-[2-(trifluoromethyl)phenyl]-2,3-dihydro-l- benzofuran-2-yl}methyl)amine

The title compound was prepared (0.135 g, 58%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-methyl-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.31 g, 0.76 mmol) and 2- (trifluoromethyl)phenylboronic acid (0.36 g, 2.28 mmol). mp 211-213 °C.

Example 288: (±)-{[7-(3-chlorophenyl)-5-methyl-2,3-dihydro-l-benzofuran- 2- yl]methyl}amine The title compound was prepared (0.028 g, 9%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-methyl-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.40 g, 1.00 mmol) and 3- chlorophenylboronic acid (0.47 g, 3.00 mmol). mp 90-93 °C.

Example 289: (±)-{[7-(3-methylphenyl)-5-methyl-2,3-dihydro-l-benzofuran- 2- yljmethyl} amine

The title compound was prepared (0.107 g, 37%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-methyl-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.40 g, 1.00 mmol) and 3- methylphenylboronic acid (0.41 g, 3.00 mmol). mp 235-237 ⁰ C.

Example 290: (±)-{[7-(4-methylphenyI)-5-methyl-2,3-dihydro-l-benzofuran- 2- yl] methyl} amine

The title compound was prepared (0.116 g, 38%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-methyl-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.40 g, 1.00 mmol) and 4- methylphenylboronic acid (0.46 g, 3.00 mmol). mp 172-173 °C.

Example 291: (±)-{[7-(4-fluorophenyl)-5-methyl-2,3-dihydro-l-benzofuran- 2- yl] methyl} amine

The title compound was prepared (0.112 g, 39%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-methyl-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.40 g, 1.00 mmol) and A- fluorophenylboronic acid (0.42 g, 3.00 mmol). mp 225-227 °C.

Example 292 : (±)-{ [7-(4-chlorophenyl)-5-methyl-2,3-dihy dro-l-benzofuran-2- yl] methyl} amine

The title compound was prepared (0.097 g, 31%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-methyl-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.40 g, 1.00 mmol) and A- chlorophenylboronic acid (0.47 g, 3.00 mmol). mp 250-252 °C.

Example 293: (±)-{[7-(4-methoxyphenyl)-5-methyl-2,3-dihydro-l-benzofuran -2- yl] methyl} amine

The title compound was prepared (0.116 g, 38%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-methyl-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.40 g, 1.00 mmol) and A- methoxyphenylboronic acid (0.49 g, 3.00 mmol). mp 207-209 °C.

Example 294: (±)-{[7-(2,3-dimethoxyphenyl)-5-methyl-2,3-dihydro-l-benzof uran-2- yl]methyl}amine

The title compound was prepared (0.164 g, 44%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-methyl-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.50 g, 1.26 mmol) and 2,3 dimethoxyphenylboronic acid (0.69 g, 3.75 mmol). mp 97-99 ⁰ C.

Example 295: (-)-{[7-(2,3-dimethoxyphenyl)-5-methyl-2,3-dihydro-l-benzofu ran-2- yl] methyl} amine

Treatment of 0.59 g of fraction 1 obtained from the chiral HPLC separation of (±)- benzyl { [7-(2,3-dimethoxyphenyl)-5-methyl-2,3-dihydro-l -benzofuran-2- yljmethyl} carbamate with trimethylsilyl iodide (1.08 g, 5.44 mmol) generally according to the procedure described for Example 158 gave 0.316 g (69%) of (-)-{[7-(2,3- dimethoxyphenyl)-5-methyl-2,3-dihydro-l-benzofuran-2-yl]meth yl}amine as a white solid, hydrochloride salt. [αβ ⁵ = -73.6 (c 10.0 in methanol); mp 120-123 °C.

Example 296: (+)-{[7-(2,3-dimethoxyphenyl)-5-methyl-2,3-dihydro-l-benzofu ran-2- yl]methyl}amine

Treatment of 0.52 g of fraction 2 obtained from the chiral HPLC separation of (±)- benzyl {[7-(2,3-dimethoxyphenyl)-5-methyl~2,3-dihydro-l-benzofuran- 2- yl]methyl}carbamate with trimethylsilyl iodide (0.956 g, 4.80 mmol) generally according to the procedure described for Example 158 afforded 0.127 g (32%) of (+)-{[7-(2,3- dimethoxyphenyl)-5-methyl-2,3-dihydro-l-benzofuran-2-yl]meth yl}amine as a white solid, hydrochloride salt, [α]" = +74.51 (c 10.0 in methanol); mp 98-100 ⁰ C.

Example 297: (±)-{[7-(2,4-dichlorophenyl)-5-methyl-2,3-dihydro-l-benzofu ran-2- yl]methyl}amine

The title compound was prepared (0.124 g, 29%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-methyl-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.50 g, 1.26 mmol) and 2,4 dichlorophenylboronic acid (0.72 g, 3.8 mmol). mp 172-173 ⁰ C.

Example 298: (-)-{[7-(2,4-dichlorophenyl)-5-methyl-2,3-dihydro-l-benzofur an-2- yl]methyl}amine

Treatment of 0.50 g of fraction 1 obtained from the chiral HPLC separation of (±)- benzyl { [7-(2,4-dichlorophenyl)-5-methyl-2,3-dihydro- 1 -benzofuran-2- yl]methyl} carbamate with trimethylsilyl iodide (0.905g, 4.52 mmol) generally according to the procedure described for Example 129 provided 0.275 g (71%) of (-)-{[7-(2,4- dichlorophenyl)-5-methyl-2,3-dihydro-l-benzofuran-2-yl]methy l}amine as a white solid, hydrochloride salt. [α]n = -8.0 (c 10.0 in methanol); mp 173-176°C.

Example 299: (+)-{[7-(2,4-dichlorophenyl)-5-methyl-2,3-dihydro-l-benzofur an-2- yl]methyl}amine

Treatment of 0.48 g of fraction 2 obtained from the chiral HPLC separation of (±)- benzyl { [7-(2,4-dichlorophenyl)-5-methyl-2,3-dihydro- 1 -benzofuran-2- yl]methyl} carbamate with trimethylsilyl iodide (0.868 g, 4.34 mmol) generally according to the procedure described for Example 129 afforded 0.254 g (68%) of (+)- { [7-(2,4- dichlorophenyl)-5-methyl-2,3-dihydro-l-benzofuran-2-yl]methy l}amine as a white solid, hydrochloride salt, [α]^ ⁵ = +7.25 (c 10.0 in methanol); mp 173-176 °C.

Example 300: (±)-{[7-(2,5-dichlorophenyl)-5-methyl-2,3-dihydro-l-benzofu ran-2- yl]methyl}amine

The title compound was prepared (0.121 g, 28%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-methyl-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.50 g, 1.26 mmol) and 2,5-dichlorophenylboronic acid (0.72 g, 3.8 mmol). mp 155-156 ⁰ C.

Example 301 : (±)-{l7-(2,6-dimethylphenyI)-5-methyl-2,3-dihydro-l-benzofu ran-2- yl]methyϊ}amine

The title compound was prepared (0.030 g, 11%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-methyl-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.50 g, 1.26 mmol) and 2,6 dimethylphenylboronic acid (0.76 g, 4.00 mmol). mp 234-235 °C.

Example 302: (±)-{[7-(2,6-dichlorophenyl)-5-methyl-2,3-dihydro-l-benzofu ran-2- yl]methyl}amine

The title compound was prepared (0.030 g, 21%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-methyl-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.56 g, 1.41 mmol) and 2,6 dichlorophenylboronic acid (2.17 g, 14.10 mmol). mp 193-195 °C.

Example 303: (-)-{[7-(2,6-dichlorophenyl)-5-methyl-2,3-dihydro-l-benzofur an-2- yl] methyl} amine

Treatment of 0.72 g of fraction 1 obtained from the chiral HPLC separation of (±)- benzyl { [7-(2,6-dichlorophenyl)-5-methyl-2,3-dihydro- 1 -benzofuran-2- yl]methyl}carbamate with trimethylsilyl iodide (1.28g, 7.20 mmol) generally according to the procedure described for Example 158 gave 0.227 g (41%) of (-)-{[7-(2,6- dichlorophenyl)-5-methyl-2,3-dihydro-l-benzofuran-2-yl]methy l}amine as a white solid, hydrochloride salt, [α]" = -28.9 (c 10.0 in methanol); mp 222-224°C.

Example 304: (+)-{[7-(2,6-dichlorophenyl)-5-methyl-2,3-dihydro-l-benzofur an-2- yl]methyl}amine

Treatment of 0.65 g of fraction 2 obtained from the chiral HPLC separation of (±)- benzyl { [7-(2,6-dichlorophenyl)-5-methyl-2,3-dihydro- 1 -benzofuran-2- yl]methyl} carbamate with trimethylsilyl iodide (1.18g, 6.00 mmol) generally according to

the procedure described for Example 158 gave 0.259 g (51%) of (+)-{[7-(2,6- dichlorophenyl)-5-methyl-2,3-dihydro-l-benzofuran-2-yl]methy l}amine as a white solid, hydrochloride; [α]^ ⁵ = +33.82 (c 10.0 in methanol); salt, mp 222-224°C.

Example 305: (±)-{[5-ethyl-7-(2-methylphenyl)-2,3-dihydro-l-benzofuran-2 - yl]methyl}amine

To a solution of 4-ethylphenol (10.0 g, 82.0 mmol) in acetonitrile (250 niL) cooled to 0 ⁰ C was slowly added N-bromosuccinimide (16.0 g, 90 mmol) and the reaction mixture was allowed to stir at 0 °C for 1 h. The solvent was removed in vacuo and the reaction mixture was diluted with ice water (500 niL) and diethyl ether (500 mL). A solid precipitate was removed via filtration and the aqueous phase was separated and extracted with ethyl ether (2 x 200 mL). The combined organic extracts were washed with saturated aqueous sodium chloride (400 mL), dried (magnesium sulfate) and the solvent was removed in vacuo to give a crude oil. Purification by flash column chromatography (silica, ethyl acetate :hexanes 1 :9) gave 8.35 g (51%). Treatment of 2-bromo-4- ethylphenol (8.35 g, 41.0 mmol) with potassium carbonate (14.3 g, 100 mmol) and allyl bromide (6.57 g, 130 mmol), followed by refluxing the resultant allyl ether in mesitylene generally according to the procedure described for Intermediate 8 provided 2-allyl-6- bromo-4-ethylphenol. Treatment of 2-allyl-6-bromo-4-ethylphenol (5.18 g, 22.0 mmol) with 3-chloroperoxybenzoic acid (8.60 g, 33.0 mmol, 77%) followed by potassium carbonate (7.4 g, 55.0 mmol) generally according to the procedure described for Intermediate 9 afforded 3.94 g (70%) of (±)-(7-bromo-5-ethyl-2,3-dihydro-l-benzofuran- 2-yl)methanol. Treatment of (±)-(7-bromo-5-ethyl-2,3-dihydro- 1 -benzofuran-2- yl)methanol (3.94 g, 15.0 mmol) withp-toluenesulfonyl chloride (3.5 g, 18.0 mol) generally according to the procedure described for Intermediate 10 gave 5.78 g (92%) of (±)-(7-bromo-5-ethyl-2,3 -dihydro- 1 -benzofuran-2-yl)methyl 4-methylbenzenesulfonate as a colorless oil. Treatment of (±)~(7-bromo-5-ethyl-2,3-dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.30 g, 0.73 mmol) and 2-methylphenylboronic acid (0.30 g, 2.19 mmol) generally according to the procedure described for Intermediate 35 afforded 0.30 g, (97%) of (±)-(5-ethyl-7-phenyl-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate. Treatment of the tosylate with sodium azide (0.23 g, 3.55 mmol) generally according to the procedure described for Intermediate 98 afforded 0.16g (77%)

of (±)-2-(azidomethyl)-5 -ethyl~7-phenyl-2,3 -dihydro- 1 -benzofuran. Treatment of (±)-2- (azidomethyl)-5 -ethyl-7-phenyl-2,3 -dihydro- 1 -benzofuran with polymer-supported triphenylphosphine (0.786 g, .869 mmol) according to the procedure described in Example 154 afforded 0.009 g (4%) of (±)-[(5-ethyl-7-ρhenyl-2,3-dihydro-l-benzofuran- 2-yl)m ethyl] amine as a white solid, hydrochloride salt, mp 198 ⁰ C (dec).

Example 306: (±)-{[5-ethyI-7-(2-chlorophenyl)-2,3-dihydro-l-benzofuran-2 - yl] methyl} amine

The title compound was prepared (0.174 g, 74%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-ethyl-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.3 g, 0.73 mmol) and 2- chlorophenylboronic acid (0.34 g, 2.19 mmol). mp 268-271 °C.

Example 307: (±)-{[5-isopropyl-7-(2-methylphenyl)-2,3-dihydro-l-benzofur an-2- yl]methyl}amine

To a solution of 4- isopropylphenol (13.38 g, 98.0 mmol) with N- bromosuccinimide (17.5 g, 98 mmol) generally according to the procedure described for Example 305 afforded 13.78 g (65%) of 2-bromo-4-isopropylphenol. Treatment of 2- bromo-4-isopropylphenol (13.74 g, 41.0 mmol) with potassium carbonate (22.0 g, 160 mmol) and allyl bromide (9.23 g, 76.8 mmol), followed by refluxing the resultant allyl ether in mesitylene generally according to the procedure described for Intermediate 8 provided 2-allyl-6-bromo-4-isopropylphenol. Treatment of 2-allyl-6-bromo-4- isopropylphenol (6.85 g, 27.0 mmol) with 3-chloroperoxybenzoic acid (7.72 g, 27.0 mmol, 77%) followed by potassium carbonate (9.3 g, 67.5.0 mmol) generally according to the procedure described for Intermediate 9 afforded 1.12 g, (17%) of (±)-(7-bromo-5- isopropyl-2,3-dihydro- 1 -benzofuran-2-yl)methanol. Treatment of (±)-(7-bromo-5- isoproρyl-2,3 -dihydro- l-benzofuran-2-yl)methanol (1.12 g, 4.6 mmol) with/?- toluenesulfonyl chloride (1.32 g, 6.9 mmol) generally according to the procedure described for Intermediate 10 gave 1.90 g (97%) of (±)-(7-bromo-5-isopropyl-2,3- dihydro- l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate as a colorless oil. Treatment of (±)-(7-bromo-5-isopropyl-2,3-dihydro-l-benzofuran-2-yl)m ethyl A- methylbenzenesulfonate (0.4 g, 0.94 mmol) and 2-rnethylphenylboronic acid (0.38 g, 2.82

mmol) generally according to the procedure described for Intermediate 35 afforded 0.19 g, (46%) of (5-isoproρyl-7-phenyl-2,3-dihydro-l-benzofuran-2-yl)methyl 4- methylbenzenesulfonate. Treatment of the tosylate with sodium azide (0.141 g, 2.17 mmol) generally according to the procedure described for Intermediate 98 afforded 0.1 Ig (83%) of (±)-2-(azidomethyl)-5-isopropyl-7-phenyl-2,3-dihydro- 1 -benzofuran. Treatment of (±)-2-(azidomethyl)-5-isopropyl-7-phenyl-2,3-dihydro-l-benz ofuran with polymer- supported triphenylphosphine (0.188 g, .716 mmol) according to the procedure described in Example 154 afforded 0.055 g (48%) of (±)-[(5-isopropyl-7-phenyl-2,3-dihydro-l- benzofuran-2-yl)m ethyl] amine as a white solid, hydrochloride salt, mp 221-222 ⁰ C (dec).

Example 308: (±)-{[5-isopropyl-7-(2-chlorophenyl)-2,3-dihydro-l-benzofur an-2- yl] methyl} amine

The title compound was prepared (0.096 g, 30%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-isopropyl-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.4 g, 0.94 mmol) and 2- chlorophenylboronic acid (0.44 g, 2.81 mmol). mp 257-260 °C.

Example 309: (±)-{[5-cyclopentyl-7-(2-methylphenyl)-2,3-dihydro-l-benzof uran-2- yl]methyl}amine To a solution of 4-cyclopentylphenol (3.0 g, 18.0 mmol) in acetonitrile (30 mL) cooled to 0 °C was slowly added N-bromosuccinimide (3.29 g, 18 mmol) generally according to the procedure described for Example 309 afforded 3.75 g (84%) of 2-bromo- 4-cyclopentylphenol Treatment of 2-bromo-4-cyclopentylphenol (3.75 g, 16.0 mmol) with potassium carbonate (5.4.0 g, 40 mmol) and allyl bromide (2.38 g, 20.8 mmol), followed by refluxing the resultant allyl ether in mesitylene generally according to the procedure described for Intermediate 8 provided 2-allyl-6-bromo-4-cyclopentylphenol. Treatment of 2-allyl-6-bromo-4-cyclopentylphenol (3.0 g, 10.0 mmol) with 3- chloroperoxybenzoic acid (3.49 g, 12.0 mmol, 77%) followed by potassium carbonate (3.7 g, 25.0 mmol) generally according to the procedure described for Intermediate 9 afforded 1.68 g, (53%) of (±)-(7-bromo-5-cyclopentyl-2,3-dihydro-l-benzofuran-2- yl)methanol. Treatment of (±)-(7-bromo-5-cyclopentyl-2,3-dihydro- 1 -benzofuran-2- yl)methanol (1.68 g, 4.6 mmol) withjo-toluenesulfonyl chloride (0.96 g, 5.0 mmol)

generally according to the procedure described for Intermediate 10 gave 1.78 g (70%) of (±)-(7-bromo-5-cyclopentyl-2,3 -dihydro- 1 -benzofuran-2-yl)methyl 4- methylbenzenesulfonate as a colorless oil. Treatment of (±)-(7~bromo-5-cyclopentyl-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.5 g, 1.1 mmol) and 2- methylphenylboronic acid (0.45 g, 3.3 mmol) generally according to the procedure described for Intermediate 35 afforded 0.51 g, (99%) of (5-cyclopentyl-7-phenyl~2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate. Treatment of the tosylate with sodium azide (0.239 g, 3.67 mmol) generally according to the procedure described for Intermediate 98 afforded 0.16g (65%) of (±)-2-(azidomethyl)-5-isopropyl-7-phenyl- 2,3-dihydro- 1 -benzofuran. Treatment of (±)-2-(azidomethyl)-5-cyclopentyl-7-phenyl-2,3- dihydro-1-benzofuran with polymer-supported triphenylphosphine (0.24 g, 0.48 mmol) according to the procedure described in Example 154 afforded 0.126 g (50%) of (±)-[(5- cyclopentyl-7-phenyl-2,3 -dihydro- l-benzofuran-2-yl)methyl] amine as a white solid, hydrochloride salt, mp 190-193 °C (dec).

Example 310: (±)-{[5-cyclopentyI-7-(2-chlorophenyl)-2,3-dihydro-l-benzof uran-2- yl] methyl} amine

The title compound was prepared (0.171 g, 42%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-cyclopentyl-2,3- dihydro- 1 -benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.50 g, 1.10 mmol) and 2- chlorophenylboronic acid (0.52 g, 3.30 mmol). mp 268-271 °C.

Example 311: (±)-2-(aminomethyl)-7-(2-methylphenyl)-2,3-dihydro-l-benzof uran-5- carbonitrile Treatment of 3-bromo-4-hydroxybenzonitrile (10.0 g, 50.0 mmol) with potassium carbonate (27.9 g, 200 mmol) and allyl bromide (7.96 g, 66.0 mmol), followed by refluxing the resultant allyl ether in mesitylene generally according to the procedure described for Intermediate 8 provided 3-allyl-5-bromo-4-hydroxybenzonitrile. Treatment of 3-allyl-5-bromo-4-hydroxybenzonitrile (4.63 g, 19.0 mmol) with 3- chloroperoxybenzoic acid (6.2 g, 35.93 mmol, 77%) followed by potassium carbonate (6.56g, 47.5 mmol) generally according to the procedure described for Intermediate 9 afforded 1.30 g (426) of (±)-7-bromo-2-(hydroxymethyl)-2,3-dihydro-l-benzofuran-5-

carbonitrile. Treatment of (±)-7-bromo-2-(hydroxyniethyl)-2,3-dihydro-l-benzofuran-5- carbonitrile (1.3 g, 5.0 mmol) with/?-toluenesulfonyl chloride (1.02 g, 5.4 mol) generally according to the procedure described for Intermediate 10 gave 1.5 g (72%) of (±)-(7- bromo-5-cyano-2,3-dihydro-l-benzofuran-2-yl)rnethyl 4-methylbenzenesulfonate as a white solid. Treatment of (±)-(7-bromo-5-cyano-2,3-dihydro- 1 -benzofuran-2-yl)methyl 4- methylbenzenesulfonate (0.30 g, 0.73 mmol) and 2-methylphenylboronic acid (0.3 g, 2.20 mmol) generally according to the procedure described for Intermediate 35 afforded 0.33 g, (99%) of (±)-[5-cyano-7-(2-methylphenyl)-2 ₅ 3-dihydro-l-benzofuran-2-yl]methyl 4- methylbenzenesulfonate. Treatment of the tosylate with sodium azide (0.26 g, 4.0 mmol) generally according to the procedure described for Intermediate 98 afforded 0.17 g (74%) of (±)-2-(azidomethyl)-7-(2-methylphenyl)-2,3-dihydro-l-benzof uran-5-carbonitrile. Treatment of the azide with polymer-supported triphenylphosphine (0.24 g, 0.67 mmol) according to the procedure described in Example 154 afforded 0.118 g (53%) of (±)-2- (aminomethyl)-7-(2-methylphenyl)-2,3-dihydro-l-benzofuran-5 -carbonitrile as a white solid, hydrochloride salt, mp 127-129 ⁰ C.

Example 312: (±)-2-(aminomethyl)-7-(2-chIorophenyl)-2,3-dihydro-l-benzof uran-5- carbonitrile

The title compound was prepared (0.27 g, 57%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-cyano-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.60 g, 1.50 mmol) and 2- chlorophenylboronic acid (0.69 g, 4.50 mmol). mp 173-175 °C.

Example 313: (±)-{[5-(trifluoromethyl)-7-(2-fluorophenyl)-2,3-dihydro-l- benzofuran-2-yl]methyl}amine

To a solution of 4-(trifluoromethyl)phenol (5.0 g, 30.86 mmol) in carbon tetrachloride (100 mL) cooled to 0 °C was added dropwise over 4 hours bromine (4.94 g, 30.86 mmol) in carbon tetrachloride (25 mL) and the reaction mixture was allowed to stir at 0 ⁰ C for 24 h. The reaction mixture was washed with 10% aqueous sodium bisulfite (100 mL) and dichloromethane (300 mL). The aqueous phase was separated and extracted with dichloromethane (2 x 100 mL). The combined organic extracts were washed with saturated aqueous sodium chloride (400 mL), dried (magnesium sulfate) and the solvent

was removed in vacuo to give a crude oil. Purification by flash column chromatography (silica, ethyl acetate :hexanes 2:8) gave 4.69 g (63%). Treatment of 2-bromo-4- (trifluoromethyl)phenol (4.69 g, 19.5 mmol) with sodium hydride (0.86g, 21.0 mmol 60%) and allyl bromide (2.5 g, 21.0 mmol), followed by refluxing the resultant allyl ether in mesitylene generally according to the procedure described for Intermediate 8 provided 2-allyl-6-bromo-4-(trifluoromethyl)phenol. Treatment of 2-allyl-6-bromo-4- (trifluoromethyl)phenol (3.66 g, 13.0 mmol) with 3-chloroperoxybenzoic acid (5.84 g, 26.0 mmol, 77%) followed by potassium carbonate (2.5 g, 19.5 mmol) generally according to the procedure described for Intermediate 9 afforded 3.5Og (91%) of (±)-(7- bromo-5-(trifluoromethyl)-2,3-dihydro-l-benzofuran-2-yl)meth anol. Treatment of (±)-(7- bromo-5-(trifluoromethyl -2,3-dihydro-l-benzofuran-2-yl)methanol (3.5 g, 11.78 mmol) with/7-toluenesulfonyl chloride (3.6 g, 17.67 mol) generally according to the procedure described for Intermediate 10 gave 5.0 g (94%) of (±)-(7-bromo-5-(trifluoromethyl)-2,3- dihydro-l-benzofuran~2-yl)methyl 4-methylbenzenesulfonate as a white solid. Treatment of (±)-(7-bromo-5-(trifluoromethyl)-2,3-dihydro- 1 -benzofuran-2-yl)methyl 4- methylbenzenesulfonate (0.30 g, 0.66 mmol) and 2-fluorophenylboronic acid (0.26 g, 2.13 mmol) generally according to the procedure described for Intermediate 35 afforded 0. 11 g, (81%) of (±)-[7-(2-fluorophenyl)-5-(trifluoromethyl)-2,3-dihydro-l-b enzofuran- 2-yl]methyl 4-methylbenzenesulfonate. Treatment of the tosylate with sodium azide (0.21 g, 3.2 mmol) generally according to the procedure described for Intermediate 98 afforded 0.16g (88%) of (±)-2-(azidomethyl)-5-(trifluoromethyl)-7-(2-fluorophenyl)- 2,3-dihydro- 1-benzofuran. Treatment of (±)-2-(azidomethyl)-5-(trifluoromethyl)-7-(2-fluorophenyl)- 2,3-dihydro-l-benzofuran with polymer-supported triphenylphosphine (0.20 g, 0.76 mmol) according to the procedure described in Example 154 afforded 0.053 g (24%) of (±)-[(5-(trifluoromethyl)-7-(phenyl)-l-2,3-dihydro-l-benzof uran-2-yl)methyl]amine as a white solid, hydrochloride salt, mp >250 °C.

Example 314: (±)-{[5-(trifluoromethyl)-7-(2-methylphenyl)-2,3-dihydro-l- benzofuran-2-yI]methyl}amine The title compound was prepared (0.148 g, 65%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-

(trifluoromethyl)-2,3-dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.30 g, 0.66 mmol) and 2-methylphenylboronic acid (0.36 g, 2.64 mmol). mp 253-255 °C.

Example 315: (±)-{[5-(trifluoromethyl)-7-(2-chlorophenyl)-2,3-dihydro-l- benzofuran-2-yl]methyl}amine

The title compound was prepared (0.27 g, 57%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5- (trifluoromethyl)-2,3-dihydro- 1 -benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.325 g, 0.72 mmol) and 2-chlorophenylboronic acid (0.169 g, 2.88 mmol). mp 192-194 °C.

Example 316: (±)-{[5-(trifluoromethyl)-7-(2-methoxyphenyI)-2,3-dihydro-l - benzofuran-2-yl]methyl}amine

The title compound was prepared (0.21 g, 87%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-

(trifluoromethyl)-2,3-dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.30 g, 0.66 mmol) and 2-methoxyphenylboronic acid (0.40 g, 2.64 mmol). mp 203-205 °C.

Example 317: (±)-{[5-(trifluoromethyl)-7-(2-(trifluoromethyl)phenyl)-2,3 -dihydro-l- benzofuran-2-yl]methyl}amine

The title compound was prepared (0.088 g, 33%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5- (trifluoromethyl)-2,3-dihydro-l -benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.30 g, 0.66 mmol) and 2-(trifluoromethyl)phenylboronic acid (0.50 g, 2.64 mmol). mp 195- 197 °C.

Example 318: (±)-{[5-(trifluoromethyl)-7-(3-methylphenyl)-2,3-dihydro-l- benzofuran-2-yl]methyl}amine

The title compound was prepared (0.092 g, 40%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-

(trifluoromethyl)-2,3-dihydro-l -benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.30 g, 0.66 mmol) and 3-methylphenylboronic acid (0.50 g, 2.64 mmol). mp >250 ⁰ C.

Example 319: (±)-{[5-(trifluoromethyl)-7-(3-fluorophenyl)-2,3-dihydro-l- benzofuran-2-yl] methyl} amine

The title compound was prepared (0.068 g, 30%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-

(trifluoromethyl)-2,3-dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.30 g, 0.66 mmol) and 3-fluorophenylboronic acid (0.50 g, 2.64 mmol). mp >250 °C.

Example 320: (±)-{[5-(trifluoromethyl)-7-(3-chlorophenyl)-2,3-dihydro-l- benzofuran-2-yl]methyl}amme

The title compound was prepared (0.102 g, 42%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5- (trifluoromethyl)-2,3-dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.30 g, 0.66 mmol) and 3-chlorophenylboronic acid (0.41 g, 2.64 mmol). 238-240 mp ⁰ C.

Example 321: (±)-{[5-(trifluoromethyl)-7-(3-methoxyphenyl)-2,3-dihydro-l - benzofuran-2-yl]methyl}amine

The title compound was prepared (0.125 g, 52%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5- (trifluoromethyl)-2,3-dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.30 g, 0.66 mmol) and 3-methoxyphenylboronic acid (0.40 g, 2.64 mmol). mp 202-204 ⁰ C.

Example 322: (±)-{[5-(trifluoromethyl)-7-(3-(trifluoromethyl)plienyl)-2, 3-dihydro-l- benzofuran-2-yl]methyl}amine The title compound was prepared (0.038 g, 14%) following the general procedure of Example 154 as a off-white solid, hydrochloride salt from (±)-(7-bromo-5- (trifluoromethyl)-2,3-dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.30 g, 0.66 mmol) and 3-(trifluoromethyl)phenylboronic acid (0.50 g, 2.64 mmol). mp 225- 227 °C.

Example 323: (±)-{[5-(trifluoromethyl)-7-(4-methylphenyl)-2,3-dihydro-l- benzofuran-2-yl]methyI}amme

The title compound was prepared (0.102 g, 46%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5- (trifluoromethyl)-2,3-dihydro-l -benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.30 g, 0.66 mmol) and 4-methylphenylboronic acid (0.36 g, 2.64 mmol). mp 248-250 °C.

Example 324: (±)-{[5-(trifluoromethyI)-7-(4-fluorophenyl)-2,3-dihydro-l- benzofuran-2-yl]methyl}amine

The title compound was prepared (0.119 g, 52%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5- (trifluoromethyl)-2,3-dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.30 g, 0.66 mmol) and 4-fluorophenylboronic acid (0.37 g, 2.64 mmol). mp >250 ⁰ C.

Example 325: (±)-{[5-(trifluoromethyl)-7-(4-chlorophenyl)-2,3-dihydro-l- benzofuran-2-yl] methyl} amine The title compound was prepared (0.036 g, 15%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5- (trifluoromethyl)-2,3-dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.30 g, 0.66 mmol) and 4-chlorophenylboronic acid (0.42 g, 2.64 mmol). mp >250 ⁰ C.

Example 326: (±)-{[5-(trifluoromethyl)-7-(4-methoxyphenyl)-2,3-dihydro-l - benzofuran-2-yl] methyl} amine

The title compound was prepared (0.130 g, 54%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5- (trifluoromethyl)-2,3-dihydro- 1 -benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.30 g, 0.66 mmol) and 4-methoxyphenylboronic acid (0.40 g, 2.64 mmol). mp 248-250 °C.

Example 327: (±)-{[5-(trifluoromethyl)-7-(4-(trifluoromethyl)phenyl)-2,3 -dihydro-l- benzofuran-2-yl]methyl}amine

The title compound was prepared (0.105 g, 40%) following the general procedure of Example 154 as white solid, hydrochloride salt from (±)-(7-bromo-5-(trifluoromethyl)- 2,3-dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.30 g, 0.66 mmol) and 4-(trifluoromethyl)phenylboronic acid (0.50 g, 2.64 mmol). mp >250 ⁰ C.

Example 328: (±)-{[7-(2,3-dimethyIphenyl)-5-(trifluoromethyl)-2,3-dihydr o-l- benzofuran-2-yl]methyl}amine

The title compound was prepared (0.124 g, 58%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-

(trifluoromethyl)-2,3-dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.30 g, 0.66 mmol) and 2,3-dimethylphenylboronic acid (0.40 g, 2.64 mmol). mp 198-200 ⁰ C.

Example 329: (±)-{[7-(2,3-difluorophenyl)-5-(trifluoromethyl)-2,3-dihydr o-l- benzofuran-2-yl]methyl}amine

The title compound was prepared (0.059 g, 25%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7~bromo-5- (trifluoromethyl)-2,3-dihydro- 1 -benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.30 g, 0.66 mmol) and 2,3-difluorophenylboronic acid (0.30 g, 1.90 mmol). mp 217-218 °C.

Example 330: (±)-{[7-(2,3-dichlorophenyl)-5-(trifluoromethyl)-2,3-dihydr o-l- benzofuran-2-yl]methyl}amine

The title compound was prepared (0.045 g, 17%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5- (trifluoromethyl)-2,3-dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.30 g ₅ 0.66 mmol) and 2,3-dichlorophenylboronic acid (0.50 g, 2.64 mmol). mp 152-155 ⁰ C.

Example 331: (±)-{[7-(2,3-dimethoxyphenyl)-5-(trifluoromethyl)-2,3-dihyd ro-l- benzofuran-2-ylJmethyI}amine The title compound was prepared (0.080 g, 31%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5- (trifluoromethyl)-2,3-dihydro- 1 -benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.30 g, 0.66 mmol) and 2,3-dimethoxyphenylboronic acid (0.48 g, 2.64 mmol). mp 178-180 °C.

Example 332: (±)-{[7-(2,4-difluorophenyl)-5-(trifluoromethyI)-2,3-dihydr o-l- benzofuran-2-yl]methyI}amine

The title compound was prepared (0.163 g, 67%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5- (trifluoromethyl)-2,3-dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.30 g, 0.66 mmol) and 2,4-difluorophenylboronic acid (0.30 g, 1.90 mmol). mp 237-239 °C.

Example 333: (±)-{[7-(2,4-dimethoxyphenyl)-5-(trifluoromethyl)-2,3-dihyd ro-l- benzofuran-2-yl] methyl} amine

The title compound was prepared (0.098 g, 38%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5- (trifluoromethyl)-2,3-dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.30 g, 0.66 mmol) and 2,4-dimethoxyphenylboronic acid (0.48 g, 2.64 mmol). mp 210-212 °C.

Example 334: (±)-{[7-(3,4-difluorophenyl)-5-(trifluoromethyl)-2,3-dihydr o-l- benzofuran-2-yl]methyl}amine

The title compound was prepared (0.063 g, 26%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5- (trifluoromethyl)-2,3-dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.30 g, 0.66 mmol) and 3,4-difluoroρhenylboronic acid (0.42 g, 2.64 mmol). mp 237-239 ⁰ C.

Example 335: (±)-{[7-(3-chloro-4-fluorophenyl)-5-(trifluoromethyl)-2,3-d ihydro-l- benzofuran-2-yl]methyl}amine

The title compound was prepared (0.044 g, 19%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5- (trifluoromethyl)-2,3-dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.30 g, 0.66 mmol) and 3-chloro-4-fluorophenylboronic acid (0.465 g, 2.64 mmol). mp >250 °C.

Example 336: (±)-{[7-(2,5-difluorophenyl)-5-(trifluoromethyl)-2,3-dihydr o-l- benzofuran-2-yl]methyl}amine

The title compound was prepared (0.063 g, 26%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-

(trifluoromethyl)-2,3-dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.30 g, 0.66 mmol) and 2,5-difluorophenylboronic acid (0.42 g, 2.64 mmol). mp >250 ⁰ C.

Example 337: (±)-{[7-(2,5-dichlorophenyl)-5-(trifluoromethyl)-2,3-dihydr o-l- benzofuran-2-yl]methyl}amine

The title compound was prepared (0.128 g, 48%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5- (trifluoromethyl)-2,3-dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.30 g, 0.66 mmol) and 2,5-dichlorophenylboronic acid (0.503 g, 2.64 mmol). mp 203-205 ⁰ C.

Example 338: (±)-{[7-(2,6-dimethylphenyl)-5-(trifluoromethyl)-2,3-dihydr o-l- benzofuran-2-yI]methyl}amine

The title compound was prepared (0.012 g, 4%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5- (trifluoromethyl)-2,3-dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.30 g, 0.66 mmol) and 2,6-dimethylphenylboronic acid (0.40 g, 2.64 mmol). mp 198-200 ⁰ C.

Example 339: (±)-{[7-(4-butylphenyl)-5-(trifluoromethyl)-2,3-dihydro-l- benzofuran-2-yl]methyI}amine The title compound was prepared (0.122 g, 48%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5- (trifluoromethyl)-2,3-dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.30 g, 0.66 mmol) and 4-butylphenylboronic acid (0.28 g, 1.57 mmol). mp 190-192 °C.

Example 340: (±)-4-[2-(aminomethyl)-5-(trifluoromethyl)-2,3-dihydro-l- benzofuran-7-yI]benzonitrile

The title compound was prepared (0.102 g, 35%) following the general procedure of Example 154 as a white solid from (±)-(7-bromo-5-(trifluoromethyl)-2,3-dihydro-l- benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.30 g, 0.66 mmol) and 4- cyanophenylboronic acid (0.23 g, 1.57 mmol). mp 238-239 °C.

Example 341 : (±)-{[7-(3-furyl)-5-(trifluoromethyl)-2,3-dihydro-l-benzofu ran-2- yl]methyl}amine

The title compound was prepared (0.053 g, 25%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5- (trifluoromethyl)-2,3-dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.30 g, 0.66 mmol) and 3-furylphenylboronic acid (0.22 g, 1.96 mmol). mp >250 °C.

Example 342: (±)-{[7-thien-3-yI-5-(trifluoromethyl)-2,3-dihydro-l-benzof uran-2- yl] methyl} amine The title compound was prepared (0.164 g, 73%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5- (trifluoromethyl)-2,3-dihydro- 1 -benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.30 g, 0.66 mmol) and 3-thienylboronic acid (0.34 g, 2.64 mmol). mp >250 °C.

Example 343: (±)-{[7-pyridm-3-yl-5-(trifluoromethyl)-2,3-diliydro-l-benz ofuran-2- yl]methyl}amine

The title compound was prepared (0.081 g, 30%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5- (trifluoromethyl)-2,3-dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.30 g, 0.66 mmol) and pyridine-3-ylboronic acid (0.24 g, 1.95 mmol). mp 200-202 °C.

Example 344: (±)-[(5,7-diphenyl-2,3-dihydro-l-benzofuran-2-yl)methyl] amine

Treatment of 3-bromo-4-hydroxybiphenyl (15.7 g, 63.0 mmol) with potassium carbonate (34.84 g, 252.0 mmol) and allyl bromide (9.15 g, 75.63 mmol), followed by refluxing the resultant allyl ether in mesitylene generally according to the procedure described for Intermediate 8 provided 3-allyl-5-bromobiphenyl-4-ol. Treatment of 3-allyl- 5-bromobiphenyl-4-ol (17.8 g, 61.5 mmol) with 3-chloroperoxybenzoic acid (31.87 g, 184.67 mmol, 77%) followed by potassium carbonate (21.27 g, 153.89 mmol) generally according to the procedure described for Intermediate 9 afforded 15.8 g (84%) of (±)-(7- bromo-5-phenyl-2,3-dihydro-l-benzofuran-2-yl)methanol. Treatment of (±)-(7-bromo-5- phenyl-2,3-dihydro-l-benzofuran-2-yl)methanol (15.8 g, 51.77 mmol) v/ithp- toluenesulfonyl chloride (14.79 g, 77.65 mmol) generally according to the procedure

described for Intermediate 10 gave 18.8 g (79%) of (±)-(7-bromo-5-phenyl-2,3-dihydro- l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate as a white solid. Treatment of (±)- (7-bromo-5-methyl-2,3-dihydro-l -benzofuran-2-yl)methyl 4-methylbenzenesulfonate (1.5 g, 3.26 mmol) and phenylboronic acid (0.59 g, 4.89 mmol) generally according to the procedure described for Intermediate 35 afforded 1.17 g, (78%) of (±)-(5,7-diphenyl~2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate. Treatment of the tosylate with sodium azide (0.342 g, 5.26 mmol) generally according to the procedure described for Intermediate 98 afforded 0.39g (91%) of (±)-2-(azidomethyl)-5,7-diphenyl-2,3- dihydro-1 -benzofuran. Treatment of (±)-2-(azidomethyl)-5,7-diphenyl-2,3-dihydro-l - benzofuran with polymer-supported triphenylphosphine (0.314 g, 1.21 mmol) according to the procedure described in Example 154 afforded 0.34 g (99%) of (±)-(5,7-diphenyl- 2,3-dihydro-l-benzofuran-2-yl)methyl amine as a white solid, hydrochloride salt, mp >250 °C.

Example 345: (±)-{[7-(2-chlorophenyl)-5-phenyI-2,3-dihydro-l-benzofuran- 2- yl]methyl}amine

The title compound was prepared (0.157 g, 39%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-methyl-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.50 g, 1.09 mmol) and 2- chlorophenylboronic acid (0.255 g, 1.63 mmol). mp >250 °C.

Example 346: (±)-{[7-(3-chlorophenyl)-5-phenyl-2,3-dihydro-l-benzofuran- 2- y I] methyl} amine

The title compound was prepared (0.166 g, 41%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-methyl-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.50 g, 1.09 mmol) and 3- chlorophenylboronic acid (0.255 g, 1.63 mmol). mp 240-242 ⁰ C.

Example 347: (±)-{[7-(4-chlorophenyl)-5-phenyl-2,3-dihydro-l-benzofuran- 2- yl]methyl}amine

The title compound was prepared (0.092 g, 22%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-methyl-2,3-

dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.50 g, 1.09 mmol) and 4- chlorophenylboronic acid (0.255 g, 1.63 mmol). mp 200-203 ⁰ C.

Example 348 : (±)-{ [7-(2-fluorophenyl)-5-phenyl-2,3-dihy dro-l-benzofuran-2- yl]methyl}amine

The title compound was prepared (0.153 g, 39%) following the general procedure of Example 154 as a light yellow solid, hydrochloride salt from (±)-(7-bromo-5-methyl- 2,3-dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.50 g, 1.09 mmol) and 2-fluorophenylboronic acid (0.228 g, 1.63 mmol). mp >250 °C.

Example 349: (±)-{[7-(3-fluorophenyl)-5-phenyI-23-dihydro-l-benzofuran-2 - yl] methyl} amine

The title compound was prepared following the general procedure of Example 154 as a light yellow solid, hydrochloride salt (0.107 g, 28%) from (±)-(7-bromo-5-methyl- 2,3-dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.50 g, 1.09 mmol) and 3-fluorophenylboronic acid (0.228 g, 1.63 mmol). mp >250 °C.

Example 350: (±)-{[7-(4-fluorophenyl)-5-phenyI-2,3-dihydro-l-benzofuran- 2- yl] methyl} amine The title compound was prepared (0.106 g, 27%) following the general procedure of Example 154 as a light yellow solid, hydrochloride salt from (±)-(7-bromo-5-methyl- 2,3-dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.50 g, 1.09 mmol) and 4-fluorophenylboronic acid (0.228 g, 1.63 mmol). mp >250 °C.

Example 351: (±)-{[7-(2-methylphenyl)-5-phenyl-2,3-dihydro-l-benzofuran- 2- yl]methyl}amine

The title compound was prepared (0.148 g, 39%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-rnethyl-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.50 g, 1.09 mmol) and 2- methylphenylboronic acid (0.222 g, 1.63 mmol). mp 225-227 ⁰ C.

Example 352: (±)-{[7-(3-methylphenyl)-5-phenyl-23-dihydro-l-benzofuran-2 - yl]methyl}amine

The title compound was prepared (0.080 g, 21%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-methyl-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.50 g, 1.09 mmol) and 3- methylphenylboronic acid (0.222 g, 1.63 mmol). mp 246-249 °C.

Example 353: (±)-{[7-(4-methylphenyl)-5-phenyl-2,3-dihydro-l-benzofuran- 2- yl]methyl}amine The title compound was prepared (0.094 g, 25%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-methyl-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.50 g, 1.09 mmol) and 4- methylphenylboronic acid (0.222 g, 1.63 mmol). mp 159-162 °C.

Example 354: (±)-{[7-(2,4-difluorophenyl)-5-phenyl-2,3-dihydro-l-benzofu ran-2- yl] methyl} amine

The title compound was prepared (0.157 g, 38%) following the general procedure of Example 154 as white solid, hydrochloride salt from (±)-(7-bromo-5-methyl-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.50 g, 1.09 mmol) and (2,4-difluorophenyl)boronic acid (0.258 g, 1.63 mmol). mp 159-162 °C.

Example 355: (±)-{[7-(2,5-dichlorophenyl)-5-phenyl-2,3-dihydro-l-benzofu ran-2- yl]methyl}amine

The title compound was prepared (0.168 g, 38%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)~(7-bromo-5-methyl-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.50 g, 1.09 mmol) and (2,5-dichlorophenyl)boronic acid (0.312 g, 1.63 mmol). mp 159-162 ⁰ C.

Example 356: (±)-{[7-(2-fluorophenyl)-5-methoxy-2,3-dihydro-l~benzofuran -2- yl] methyl} amine

The title compound was prepared (0.121 g, 49%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-methoxy-2,3-

dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.50 g, 1.21 mmol) and 2- fluorophenylboronic acid (0.68 g, 4.84 mmol). mp >250 ⁰ C.

Example 357: (±)-{[7-(2-chlorophenyl)-5-methoxy-2,3-dihydro-l-benzofuran -2- yl]methyl}amine

The title compound was prepared (0.121 g, 46%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-methoxy-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.50 g, 1.21 mmol) and 2- chlorophenylboronic acid (0.75 g, 4.84 mmol). mp 179-181 ⁰ C.

Example 358: (±)-{[7-(2-methyIphenyl)-5-methoxy-2,3-dihydro-l-benzofuran -2- yl]methyl}amine

The title compound was prepared (0.118 g, 48%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-methoxy-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.50 g, 1.21 mmol) and 2- methylphenylboronic acid (0.66 g, 4.84 mmol). mp 187-189 °C.

Example 359: (±)-{[7-(2-methoxyphenyl)-5-methoxy-2,3-dihydro-l-benzofura n-2- yl]methyl}amine The title compound was prepared (0.181 g, 33%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-methoxy-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (1.0 g, 2.42 mmol) and 2- methoxyphenylboronic acid (1.55 g, 9.68 mmol). mp 190-192 ⁰ C.

Example 360: (±)-{[5-methoxy-7-(3-thienyl)-2,3-dihydro-l-benzofuran-2- yl] methyl} amine

The title compound was prepared (0.110 g, 46%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-methoxy-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.50 g, 1.21 mmol) and 3- thienylboronic acid (0.62 g, 4.84 mmol). mp 230-232 ⁰ C.

Example 361: (±)-{[7-(2,3-difluorophenyl)-5-methoxy-2,3-dihydro-l-benzof uran-2- yl] methyl} amine

The title compound was prepared (0.141 g, 54%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-methoxy-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.50 g, 1.26 mmol) and 2,3 difluorophenylboronic acid (0.76 g, 4.84 mmol). mp 224-226 ⁰ C.

Example 362: (±)-{[7-(2,3-dichlorophenyl)-5-methoxy-2,3-dihydro-l-benzof uran-2- yl]methyl}amine The title compound was prepared (0.087 g, 30%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-methoxy-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.50 g, 1.26 mmol) and 2,3 dichlorophenylboronic acid (0.92 g, 4.84 mmol). mp 159-161 ⁰ C.

Example 363: (±)-{[7-(2,3-dimethylphenyl)-5-methoxy-2,3-dihydro-l-benzof uran-2- yl]methyl} amine

The title compound was prepared (0.132 g, 52%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-methoxy-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.50 g, 1.26 mmol) and 2,3 dimethylphenylboronic acid (0.70 g, 4.84 mmol). mp 129-130 ⁰ C.

Example 364: (±)-{[7-(2,4-difluorophenyl)-5-methoxy-2,3-dihydro-l-benzof uran-2- yl]methyl}amine

The title compound was prepared (0.164 g, 63%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-methoxy-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.50 g, 1.26 mmol) and 2,4 difluorophenylboronic acid (0.76 g, 4.84 mmol). mp 226-228 °C.

Example 365: (±)-{[7-(2,4-dichlorophenyl)-5-methoxy-2,3-dihydro-l-benzof uran-2- yl]methyl}amine

The title compound was prepared (0.091 g, 32%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-methoxy-2,3-

dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.50 g, 1.26 mmol) and 2,4 dichlorophenylboronic acid (0.92 g, 4.84 mmol). mp 180-182 °C.

Example 366: (±)-{[7-(2,5-difluorophenyl)-5-methoxy-2,3-dihydro-l-benzof uran-2- yl]methyl}amine

The title compound was prepared (0.148 g, 56%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7~bromo-5-methoxy-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.50 g, 1.26 mmol) and 2,5 difluorophenylboronic acid (0.76 g, 4.84 mmol). mp 118-120 °C.

Example 367: (±)-{[7-(2,5-dichlorophenyl)-5-methoxy-2,3-dihydro-l-benzof uran-2- yl]methyl}amine

The title compound was prepared (0.048 g, 16%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-methoxy-2,3~ dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.50 g, 1.26 mmol) and 2,5 dichlorophenylboronic acid (0.92 g, 4.84 mmol). mp 140-142 °C.

Example 368: (+)-{[7-(2,5-dichlorophenyl)-5-methoxy-2,3-dihydro-l-benzofu ran-2- yl]methyl}amine Treatment of 0.50 g of fraction 1 obtained from the chiral HPLC separation of (±)- benzyl { [7-(2,5-dichlorophenyl)-5-methoxy-2,3-dihydro- 1 -benzofuran-2- yl]methyl}carbamate with hydrogen bromide (14 mL, 30 wt.% in acetic acid) generally according to the procedure described for Example 245 gave 0.297 g (75%) of (+)-{[7- (2,5-dichlorophenyl)-5-methoxy-2,3-dihydro-l-benzofuran-2-yl ]methyl}amine as a white solid, hydrochloride salt. [<X] _D = +6.62 (c 10.0 in methanol); mp 148-150 ⁰ C.

Example 369: (-)-{[7-(2,5-dichlorophenyl)-5-methoxy-2,3-dihydro-l-benzofu ran-2- yl]methyl}amine

Treatment of 0.135 g of fraction 2 obtained from the chiral HPLC separation of (±)-benzyl {[7-(2,5-dichloroρhenyl)-5-methoxy-2,3-dihydro-l-benzofuran -2- yl]methyl} carbamate with hydrogen bromide (3 mL, 30 wt.% in acetic acid) generally according to the procedure described for Example 245 gave 0.047g (44%) of (-)-{[7-(2,5-

dichlorophenyl)-5-methoxy-2,3-dihydro-l-benzofuran-2-yl]m ethyl}amine as a white solid, hydrochloride salt, [α]" = -6.73 (c 10.0 in methanol); nip 148-150 °C.

Example 370: (±)-{[7-(2,5-dimethylphenyl)-5-methoxy-2,3-dihydro-l-benzof uran-2- yl]methyl}amine

The title compound was prepared (0.134 g, 53%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-methoxy-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.50 g, 1.26 mmol) and 2,5 dimethylphenylboronic acid (0.70 g, 4.84 mmol). mp 214-216 °C.

Example 371: (±)-{[7-(2,5-dimethoxyphenyl)-5-methoxy-2,3-dihydro-l-benzo furan- 2-yl]methyl}amine

The title compound was prepared (0.070 g, 24%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-methoxy-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.50 g, 1.26 mmol) and 2,5 dimethoxyphenylboronic acid (0.88 g, 4.84 mmol). mp 128-130 °C.

Example 372: (±)-{[7-(5-chloro-2-methoxyphenyl)-5-methoxy-2,3-dihydro-l- b enzofu r an-2-y 1] methyl} amine The title compound was prepared (0.169 g, 60%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-methoxy-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.50 g, 1.26 mmol) and 5- chloro-2-methoxyphenylboronic acid (0.90 g, 4.84 mmol). mp 172-174 °C.

Example 373: (±)-{[7-(3-chloro-4-fluorophenyl)-5-methoxy-2,3-dihydro-l- benzofuran-2-yl]methyl}amine

The title compound was prepared (0.178 g, 65%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-methoxy-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.50 g, 1.26 mmol) and 3- chloro-4-fluorophenylboronic acid (0.84 g, 4.84 mmol). mp 220-222 °C.

Example 374: (±)-{[7-(2,6-dimethylphenyl)-5-methoxy-2,3-dihydro-l-benzof uran-2- yl]methyl}amine

The title compound was prepared (0.170 g, 67%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-(7-bromo-5-methoxy-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.50 g, 1.26 mmol) and 2,6 dimethylphenylboronic acid (0.92 g, 4.84 mmol). mp 212-214 °C.

Example 375: (±)-{[7-fluoro-5-(2-methyIphenyl)-2,3-dihydro-l-benzofuran- 2- yl] methyl} amine Treatment of 4-bromo-2-fluorophenol (25.0 g, 130.9 mmol) with potassium carbonate (72.35 g, 523.53 mmol) and allyl bromide (19.00 g, 157.06 mmol), followed by refluxing the resultant allyl ether in mesitylene generally according to the procedure described for Intermediate 8 provided 2-allyl-4-bromo-6-fluorophenol. Treatment of 2- allyl-4-bromo-6-fluorophenol (25.6 g, 110.8 mmol) with 3-chloroperoxybenzoic acid (57.36 g, 332.38 mmol, 77%) followed by potassium carbonate (38.28 g, 277.0 mmol) generally according to the procedure described for Intermediate 9 afforded 19.1 g (70%) of (±)-(7-fluoro-5-bromo-2,3-dihydro-l-benzofuran-2-yl)methano l. Treatment of (±)-(7- fluoro-5-bromo-2,3-dihydro-l-benzofuran-2-yl)methanol (18.61 g, 75.3 mmol) with/?- toluenesulfonyl chloride (17.22 g, 90.34 mmol) generally according to the procedure described for Intermediate 10 gave 22.6 g (75%) of (±)-(7-fluoro-5-bromo-2,3-dihydro-l- benzofuran-2-yl)m ethyl 4-methylbenzenesulfonate as a white solid. Treatment of (±)-(7- fluoro-5-bromo-2,3-dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.5 g, 1.25 mmol) and 2-methylphenylboronic acid (0.254 g, 1.87 mmol) generally according to the procedure described for Intermediate 35 afforded 0.282 g, (55%) of (±)-([7-fluoro-5- (2-methylphenyl)-2,3-dihydro- 1 -benzofuran-2-yl] methyl 4-methylbenzenesulfonate.

Treatment of the tosylate with sodium azide (0.19 g, 3.0 mmol) generally according to the procedure described for Intermediate 98 afforded 0.17g (99%) of (±)-2-(azidomethyl)-7- fiuoro-5-(2-methylphenyl)-2,3-dihydro-l-benzofuran. Treatment of (±)-2-(azidomethyl)- 7-fluoro-5-(2-methylphenyl)-2,3-dihydro-l-benzofuran with polymer-supported triphenylphosphine (0.30 g, 3.0 mmol) according to the procedure described in Example 154 afforded 0.038 g (22%) of (±)-([7-fmoro-5-(2-methylphenyl)-2,3-dihydro-l- benzofuran-2-yl]methyl] amine as a white solid, hydrochloride salt, mp >250 °C.

Example 376: (±)-{[7-fluoro-5-(2-chlorophenyl)-2,3-d»hydro-l-benzofuran -2- yl] methyl} amine

The title compound was prepared (0.026 g, 24%) following the general procedure of Example 154 as a white solid, hydrochloride salt from of (±)-(7-fluoro-5-bromo-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate. (0.50 g, 1.25 mmol) and 2- chlorophenylboronic acid (0.292 g, 1.89 mmol). mp >250 °C.

Example 377: (±)-{[7-fluoro-5-(2-fluorophenyl)-2,3-dihydro-l-benzofuran- 2- yl]methyl}amine

The title compound was prepared (0.055 g, 38%) following the general procedure of Example 154 as a white solid, hydrochloride salt from of (±)-(7-fluoro-5-bromo-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate. (0.50 g, 1.25 mmol) and 2- fluorophenylboronic acid (0.292 g, 1.89 mmol). mp >250 °C.

Example 378: (±)-({7-fluoro-5-[2-(trifluoromethyl)phenyl]-2,3-dihydro-l- benzofuran-2-yl}methyl)amine

The title compound was prepared (0.059 g, 38%) following the general procedure of Example 154 as a white solid, hydrochloride salt from of (±)-(7-fluoro-5-bromo-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate. (0.50 g, 1.25 mmol) and

[2-(trifluoromethyl)phenyl]boronic acid (0.355 g,1.89 mmol). mp 189-194 °C (dec).

Example 379: (±)~{[7-fluoro-5-(2-methoxyphenyl)-2,3-dihydro-l-benzofuran -2- yl] methyl} amine The title compound was prepared (0.050 g, 38%) following the general procedure of Example 154 as a white solid, hydrochloride salt from of (±)-(7-fiuoro-5-bromo-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate. (0.50 g, 1.25 mmol) and 2- methoxyphenylboronic acid (0.284 g, 1.89 mmol). mp 203-207 °C (dec).

Example 380: (±)-{[7-fluoro-5-(3-methylphenyl)-2,3-dihydro-l-benzofuran- 2- yl]methyl}amine

The title compound was prepared (0.057 g, 40%) following the general procedure of Example 154 as a white solid, hydrochloride salt from of (±)-(7-fluoro-5-bromo-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate. (0.50 g, 1.25 mmol) and 3- methylphenylboronic acid (0.254 g, 1.89 mmol). mp >250 °C.

Example 381: (±)-{[7-fluoro-5-(3-fluorophenyl)-2,3-dihydro-l-benzofuran- 2- yl] methyl} amine

The title compound was prepared (0.071 g, 52%) following the general procedure of Example 154 as a white solid, hydrochloride salt from of (±)-(7-fluoro-5-bromo-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate. (0.50 g, 1.25 mmol) and 3- fluorophenylboronic acid (0.292 g, 1.89 mmol). mp >250 °C.

Example 382: (±)-{[7-fluoro-5-(3-chIorophenyl)-2,3-dihydro-l-benzofuran- 2- yl]methyl}amine The title compound was prepared (0.065 g, 44%) following the general procedure of Example 154 as a white solid, hydrochloride salt from of (±)-(7-fluoro-5-bromo-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate. (0.50 g, 1.25 mmol) and 3- chlorophenylboronic acid (0.292 g, 1.89 mmol). mp >250 °C.

Example 383: (±)-({7-fluoro-5-[3-(trifluoromethyl)phenyl]-2,3-dihydro-l- benzofuran-2-yl}methyl)amine

The title compound was prepared (0.055 g, 37%) following the general procedure of Example 154 as a white solid, hydrochloride salt from of (±)-(7-fluoro-5-bromo-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate. (0.50 g, 1.25 mmol) and 3- (trifluoromethyl)ρhenylboronic acid (0.355 g, 1.89 mmol). mp >250 °C.

Example 384: (±)-{[7-fluoro-5-(3-methoxyphenyl)-2,3-dihydro-l-benzofuran -2- yl] methyl} amine

The title compound was prepared (0.042 g, 32%) following the general procedure of Example 154 as a white solid, hydrochloride salt from of (±)-(7-fluoro-5-bromo-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate. (0.50 g, 1.25 mmol) and 3- methoxyphenylboronic acid (0.284 g, 1.89 mmol). mp >250 °C.

Example 385: (±)-{[7-fluoro-5-(4-methylphenyl)-2,3-dihydro-l-benzofuran- 2- yl]methyl} amine

The title compound was prepared (0.061 g, 50%) following the general procedure of Example 154 as a white solid, hydrochloride salt from of (±)-(7-fluoro-5-bromo~2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate. (0.50 g, 1.25 mmol) and A- methylphenylboronic acid (0.254 g, 1.89 mmol). mp >250 °C.

Example 386: (±)-{[7-fluoro-5-(4-chlorophenyl)-2,3-dihydro-l-benzofuran- 2- yl]methyl}amine

The title compound was prepared (0.085 g, 55%) following the general procedure of Example 154 as a white solid, hydrochloride salt from of (±)-(7-fluoro-5-bromo-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate. (0.50 g, 1.25 mmol) and A- chlorophenylboronic acid (0.292 g, 1.89 mmol). mp >250 °C.

Example 387: (±)-{[7-fluoro-5-(4-fluorophenyl)-2,3-dihydro-l-benzofuran- 2- yl]methyl}amine

The title compound was prepared (0.060 g, 47%) following the general procedure of Example 154 as a white solid, hydrochloride salt from of (±)-(7-fluoro-5-bromo-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate. (0.50 g, 1.25 mmol) and A- fluorophenylboronic acid (0.292 g, 1.89 mmol). mp >250 ⁰ C.

Example 388: (±)-({7-fluoro-5-[4-(trifluoromethyl)phenyl]-2,3-dihydro-l- benzofuran-2-yI}methyl)amine The title compound was prepared (0.041 g, 26%) following the general procedure of Example 154 as a white solid, hydrochloride salt from of (±)-(7-fluoro-5-bromo-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate. (0.50 g, 1.25 mmol) and [4-(trifluoromethyl)phenyl]boronic acid (0.355 g, 1.89 mmol). mp >250 °C.

Example 389: (±)-{[7-fluoro-5-(4-methoxyphenyl)-2,3-dihydro-l-benzofuran -2- yl]methyl}amine

The title compound was prepared (0.66 g, 51%) following the general procedure of Example 154 as a white solid, hydrochloride salt from of (±)-(7-fluoro-5-bromo-2,3- dihydro-l-benzofuran-2-yl)methyl 4-methylbenzenesulfonate. (0.50 g, 1.25 mmol) and 4- methoxyphenylboronic acid (0.284 g, 1.89 mmol). mp >250 °C.

Example 390: (±)-N-{[7-(2,6-dichlorophenyl)-2,3-dihydro-l-benzofuran-2- yl]methyl}ethanamine

To a solution of (±)-7-(2,6-dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl 4- methylbenzenesulfonate (0.2 g, 0.46 mmol) in dimethylsulfoxide (5 mL) was added ethylamine (0.20 g, 4.4 mmol) and the reaction mixture was allowed to stir at 60 °C for 12 h. The reaction was diluted with water (10 mL) and ethyl acetate (2 x 10 mL). The combined organic layers were washed with water (3 x 20 mL) and saturated aqueous sodium chloride (20 mL), dried (magnesium sulfate) and the solvent was removed in vacuo to give an oil. The oil was re-dissolved in isopropanol (0.5 mL) and hydrogen chloride (0.5 mL, 1.0 M in diethyl ether) was added. The resulting precipitate was filtered, washed (diethyl ether), to give 0.084 g (57%) of (±)-N-{[7-(2,6-dichlorophenyl)- 2,3-dihydro-l-benzofuran-2-yl]methyl}ethanamine as a white solid, hydrochloride salt, mp 195-197 °C.

Example 391: (±)-N-{[7-(2,6-dichlorophenyl)-2,3-dihydro-l-benzofuran-2- yl]methyl}cyclopropanamine

The title compound was prepared (0.057 g, 39%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-7-(2,6-dichlorophenyl)-2,3- dihydro-l-benzofuran-2-yl 4-methylbenzenesulfonate (0.2 g, 0.46 mmol) and cyclopropylamine (0.254 g, 4.40 mmol). mp 182- 184 °C.

Example 392: (±)-N-{[7-(2,6-dichlorophenyl)-2,3-dihydro-l-benzofuran-2- yl]methyl}cyclobutanamme

The title compound was prepared (0.077 g, 39%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-7-(2,6-dichlorophenyl)-2,3- dihydro-l-benzofuran-2-yl 4-methylbenzenesulfonate (0.2 g, 0.46 mmol) and cyclobutylamine (0.317 g, 4.40 mmol). mp 185-188 °C.

Example 393: (±)-N-{[7-(2,6-dichlorophenyI)-2,3-dihydro-l-benzofuran-2- yI]methyl}propan-2-amine

The title compound was prepared (0.054 g, 35%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-7-(2,6-dichlorophenyl)-2,3- dihydro-l-benzofuran-2-yl 4-methylbenzenesulfonate (0.2 g, 0.46 mmol) and isopropylamine (0.258g, 4.40 mmol). mp 182-184 °C.

Example 394: No compound

Example 395: (±)-{[6-fluoro-7-(2-methylphenyl)-2,3-dihydro-l-benzofuran- 2- yl]methyl}amine

Treatment of 1 -bromo-2-methylbenzene (10.06 g, 58.84 mmol) with (2-fluoro-6- methyoxyphenyl)boronic acid (5.0 g, 29.42 mol tetrakis(triphenylphosphine)palladium(0) (2.5 g, 2.16 mmol), and sodium carbonate (6.2 g, 58.84 mmol) generally according to the procedure described for Intermediate 37 provided 2.35 g (37%) of 6-fluoro-2'- methylbiphenyl-2-yl methyl ether. A solution of 6-fluoro-2'-methylbiphenyl-2-yl methyl ether (2.35 g, 10.86 mmol) in hydrogen bromide (40 mL, 30 wt.% in acetic acid) was heated to 55 °C for 12h. The reaction mixture was concentrated under in vacuo and the crude residue diluted with ethyl acetate (200 mL). The organic layer was carefully extracted with saturated bicarbonate solution (3 X 200 mL) was dried (magnesium sulfate), and the solvent was removed in vacuo to provide a crude oil. Treatment of 6- fluoro-2'-methybiphenyl -2-ol (2.17 g, 10.84 mmol) with sodium hydride (0.65 g, 16.26 mmol, 60 wt. %) and allyl bromide (0.96 g, 16.26 mmol), followed by refmxing the resultant allyl ether in mesitylene generally according to the procedure described for

Intermediate 8 provided 3-allyl-6-fluoro-2'-methylbiphenyl-2-ol. Treatment of 3-allyl-6- fluoro-2'-methylbiphenyl-2-ol (1.77g, 7.3 mmol) with 3-chloroperoxybenzoic acid (3.2 g, 10.96 mmol, 77%) followed by potassium carbonate (1.2 g, 8.76 mmol) generally according to the procedure described for Intermediate 9 afforded 1.5 g (80%) of (±)-[6- fluoro-7-(2-methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]meth anol. Treatment of (±)-[6- fluoro-7-(2-methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]meth anol (1.5g, 5.81 mmol) withjp-toluenesulfonyl chloride (1.66 g, 8.71 mol) generally according to the procedure

described for Intermediate 10 gave 2.17 g (90%) of (±)-[6-fluoro-7-(2-methylphenyl)-2,3- dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate as a white solid. Treatment of (±)-[6-fluoro-7-(2-methylphenyl)-2,3-dihydro-l-benzofuran-2 -yl]methyl 4- methylbenzenesulfonate (0.23 g, 0.56 mmol) with sodium azide (0.23 g, 3.54 mmol) generally according to the procedure described for Intermediate 98 afforded 0.135 g, (86%) of (±)-2-(azidomethyl)- 6-fluoro-7-(2-methylphenyl)-2,3-dihydro-l -benzofuran. Treatment of (±)-2-(azidomethyl)- 6-fluoro-7-(2-methylphenyl)-2,3-dihydro-l- benzofuran (0.135 g, 0.4 mmol) in tetrahydrofuran (10 niL) with polymer-supported triphenylphosphine (0.30 g, 0.9 mmol) generally according to the procedure described for Example 154 provided 0.11 g (67%) of (±)- { [6-fluoro-7-(2-methylρhenyl)-2,3-dihydro- 1 - benzofuran-2-yl]methyl} amine as a white solid, hydrochloride salt, mp 216-218 °C.

Example 396: (+)-{[6-fluoro-7-(2-methylphenyl)-2,3-dihydro-l-benzofuran-2 - yl]methyl}amine Treatment of 0.66 g of fraction 1 obtained from the chiral HPLC separation of (±)- benzyl { [6-fluoro-7-(2-methylphenyl)-2,3 -dihydro- 1 -benzofuran-2-yl]methyl } carbamate with hydrogen bromide (5 mL, 30 wt.% in acetic acid) generally according to the procedure described for Example 245 gave 0.276 g (76%) of (+)-{[6-fluoro-7-(2- methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}amine as a white solid, hydrochloride salt, mp 216-218 ⁰ C.

Example 397: (-)-{[6-fluoro-7-(2-methylphenyl)-2,3-dihydro-l-benzofuran-2 - yl] methyl} amine

Treatment of 0.66 g of fraction 2 obtained from the chiral HPLC separation of (±)- benzyl { [(6-fluoro-7-(2-methylphenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methyl} carbamate with hydrogen bromide (5 mL, 30 wt.% in acetic acid) generally according to the procedure described for Example 245 gave 0.192 g (52%) of (-)-{[6-fluoro-7-(2- methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}amine as a white solid, hydrochloride salt, mp 216-218 °C.

Example 398: (±)-{[7-(2-chlorophenyl)-6-fluoro-2,3-dihydro-l-benzofuran- 2- yl]methyl}amine

Treatment of l-bromo-2-chlorobenzene (5.63 g, 29.4 mmol) with (2-fluoro-6- methyoxyphenyl)boronic acid (5.0 g, 29.42 mol) generally according to the procedure described for Intermediate 37 afforded 2.Og (29%) of 6-fluoro-2'-chlorobiphenyl-2-yl methyl ether. Treatment of 6-fluoro-2'-chlorobiphenyl-2-yl methyl ether with hydrogen bromide (50 mL, 30 wt.% in acetic acid) generally according to the procedure described for Example 395 afforded a brown oil. The oil was reacted with sodium hydride (0.34 g, 14.35 mmol) and allyl bromide (1.74 g, 14.35 mmol) followed by refluxing the resultant allyl ether in mesitylene generally according to the procedure described for Intermediate 8 to provide 3-allyl-6-chloro-2'-chlorobiphenyl-2-ol. Treatment of 3-allyl-6-fluoro-2'- methylbiphenyl-2-ol (1.2 g, 4.56 mmol) with w-chloroperoxybenzoic acid (2.36 g, 13.68 mmol, 77%) and potassium carbonate (1.575 g, 11.4 mmol) generally according to the procedure described for Intermediate 9 afforded 0.7 g (55%) of (±)-[7-(2-chlorophenyl)- 6-fluoro-2,3-dihydro- 1 -benzofuran-2-yl] methanol. Treatment (±)-[7-(2-chlorophenyl)-6- fluoro-2,3-dihydro-l-benzofuran-2-yl]methanol (1.5g, 5.81 mmol) with p-toluenesulfonyl chloride (1.66 g, 8.71 mol) generally according to the procedure described for

Intermediate 10 gave 0.9 g (82%) of (±)-[6-fluoro-7-(2-chlorophenyl)-2,3-dihydro-l- benzofuran-2-yl]methyl 4-methylbenzenesulfonate as a white solid. Treatment of (±)-[6- fluoro-7-(2-chlorophenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methyl 4- methylbenzenesulfonate (0.50 g, 1.15 mmol) with sodium azide (0.4 g, 6.15 mmol) generally according to the procedure described for Intermediate 98 afforded 0.35 g, (99%) of (±)-2-(azidomethyl)-7-(2-chlorophenyl)-6-fluoro-2,3-dihydro - 1 -benzofuran. Treatment of (±)-2-(azidomethyl)-7-(2-chlorophenyl)-6-fluoro-2,3-dihydro -l-benzofuran (0.35g, 1.15 mmol) in tetrahydrofuran (10 mL) with polymer-supported triphenylphosphine (0.60 g, 2.3 mmol) generally according to the procedure described for Example 154 provided 0.17Og (47%) of (db)- { [6-fluoro-7-(2-chlorophenyl)-2,3-dihydro- 1 -benzofuran-2- yl]methyl} amine as a white solid, hydrochloride salt, mp 248-250 °C.

Example 399: (±)-{[6-chloro-7-(2-methylphenyl)-2,3-dihydro-l-benzofuran- 2- yl]methyl}amine Treatment of 1 -bromo-2-methylbenzene (5.0 g, 26.88 mmol) with (2-chloro-6- methyoxyphenyl)boronic acid (13.8 g, 80.6 mol) generally according to the procedure described for Intermediate 37 afforded 3.85g (62%) of 6-chloro-2'-methylbiphenyl-2-yl

methyl ether. Treatment of 6-chloro-2'-methylbiphenyl-2-yl methyl ether with hydrogen bromide (100 mL, 30 wt.% in acetic acid) generally according to the procedure described for Example 395 afforded brown oil. The oil was reacted with sodium hydride (0.61 g, 25.38 mmol) and allyl bromide (3.07 g, 25.38 mmol) followed by refluxing the resultant allyl ether in mesitylene generally according to the procedure described for Intermediate 8 provided 3-allyl-6-chloro-2'-methylbiphenyl-2-ol. Treatment of 3-allyl-6-chloro-2'- methylbiphenyl-2-ol (4.38 g, 16.92 mmol) with rø-chloroperoxybenzoic acid (4.38 g, 25.38 mmol, 77%) and potassium carbonate (2.81 g, 20.30 mmol) generally according to the procedure described for Intermediate 9 afforded 2.4 g (52%) of (±)-[7-(2- methylphenyl)-6-chloro-2,3-dihydro-l-benzofuran-2-yl]methano l. Treatment (±)-[7-(2~ methylphenyl)-6-chloro-2,3-dihydro-l-benzofuran-2-yl]methano l (2.4 g, 8.73 mmol) with jσ-toluenesulfonyl chloride (2.5O g, 13.1 mmol) generally according to the procedure described for Intermediate 10 gave 3.2 g (85%) of (±)-[6-chloro-7-(2-methylphenyl)-2,3- dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate as a colorless oil. Treatment of (±)-[6-chloro-7-(2-methylphenyl)-2,3-dihydro-l-benzofuran-2 -yl]methyl 4- methylbenzenesulfonate (0.21 g, 0.49 mmol) with sodium azide (0.35 g, 5.38 mmol) generally according to the procedure described for Intermediate 98 afforded 0.14 g, (99%) of (±)-2-(azidomethyl)-7-(2-methylphenyl)-6-chloro-2,3-dihydro - 1 -benzofuran. Treatment of (±)-2-(azidomethyl)-7-(2-methylphenyl)-6-chloro-2,3 -dihydro- 1 -benzofuran (0.14g, 0.468 mmol) in tetrahydrofuran (10 mL) with polymer-supported triphenylphosphine (0.24 g, 0.936 mmol) generally according to the procedure described for Example 154 provided 0.028 g (18%) of (±)-{[6-chloro-7-(2-methylphenyl)-2,3- dihydro-l-benzofuran-2-yl] methyl} amine as a white solid, hydrochloride salt, mp 204- 206 °C.

Example 400: (±)-{[6-chloro-7-(2-chIorophenyl)-2,3-dihydro-l-benzofuran- 2- yl]methyl}amine

Treatment of l-bromo-2-chlorobenzene (5.0 g, 26.88 mmol) with (2-chloro-6- methyoxyphenyl) boronic acid (15.6 g, 80.64 mol) generally according to the procedure described for Intermediate 37 afforded 5.O g (73%) of 6-chloro-2'-chlorobiphenyl-2-yl methyl ether. Treatment of 6-chloro-2'-methylbiphenyl-2-yl methyl ether with hydrogen bromide (60 mL, 30 wt.% in acetic acid) generally according to the procedure described

for Example 395 afforded a brown oil. The oil was reacted with sodium hydride (1.05 g, 26.35 mmol) and allyl bromide (3.19 g, 26.35 mmol) followed by refluxing the resultant allyl ether in mesitylene generally according to the procedure described for Intermediate 8 provided 3-allyl-6-chloro-2'-chlorobiphenyl-2-ol. Treatment of 3-allyl-6-chloro-2'- chlorobiphenyl-2-ol (2.8 g, 10.03 mmol) with w-chloroperoxybenzoic acid (4.6 g, 15.0 mmol, 77%) and potassium carbonate (1.6 g, 12.0 mmol) generally according to the procedure described for Intermediate 9 afforded 2.2 g (74%) of (±)-[7-(2-chlorophenyl)- 6-chloro-2,3-dihydro-l-benzofuran-2-yl]methanol. Treatment (±)-[7-(2-chlorophenyl)-6- chloro-2,3-dihydro-l-benzofuran-2-yl]methanol (1.6 g, 5.42 mmol) withp- toluenesulfonyl chloride (1.55 g, 8.13 mmol) generally according to the procedure described for Intermediate 10 gave 2.1 g (86%) of (±)-[6-chloro-7-(2-chlorophenyl)-2,3- dihydro-l-benzofuran-2-yl] methyl 4-methylbenzenesulfonate as a colorless oil. Treatment of (±)-[6-chloro-7-(2-chlorophenyl)-2,3-dihydro-l-benzofuran-2 -yl]methyl 4- methylbenzenesulfonate (0.2 g, 0.44 mmol) with sodium azide (0.2 g, 3.08 mmol) generally according to the procedure described for Intermediate 98 afforded 0.14 g, (99%) of (±)-2-(azidomethyl)-7-(2-chlorophenyl)-6-chloro-2,3-dihydro -l -benzofuran. Treatment of (±)-2-(azidomethyl)-7-(2-chlorophenyl)-6-chloro-2,3-dihydro -l-benzofuran (0.14g, 0 .43 mmol) in tetrahydrofuran (10 mL) with polymer-supported triphenylphosphine (0.3 g, 1.14 mmol) generally according to the procedure described for Example 154 provided 0.036 g (24%) of (±)-{[6-chloro-7-(2-chlorophenyl)-2,3-dihydro-l-benzofuran- 2- yl] methyl} amine as a white solid, hydrochloride salt, mp 221-223 °C.

Example 401: (±)-{[6-fluoro-7-(2-methylphenyl)-2,3-dihydro-l-benzofuran- 2- yl]methyl}methylamine The title compound was prepared (0.053 g, 72%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[6-fluoro-7-(2- methylphenyl)-2,3-dihydro-l-benzofuran-2-yl] methyl 4-methylbenzenesulfonate (0.1 g, 0.24 mmol) and methylamine (0.31 g, 10.0 mmol). mp 200-202 °C.

Example 402: (±)-{[6-fluoro-7-(2-chlorophenyl)-2,3-dihydro-l-benzofuran- 2- yl]methyl}methylamine

The title compound was prepared (0.12 g, 40%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[6-fluoro-7-(2- chlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.4 g, 0.92 mmol) and methylamine (0.55 g, 17.7 mmol). mp 170-173 °C.

Example 403: (±)-{[6-chloro-7-(2-methylphenyl)-2,3-dihydro-l-benzofuran- 2- yl]methyl}methylamine

The title compound was prepared (0.02 g, 27%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[6-chloro~7-(2- methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.1 g, 0.23 mmol) and methylamine (0.24 g, 7.8 mmol). mp 158-160 ⁰ C.

Example 404: (±)-{[6-chloro-7-(2-chlorophenyl)-2,3-dihydro-l-benzofuran- 2- yl]methyl}methylamine The title compound was prepared (0.056g, 73%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[6-chloro-7-(2- chlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.1 g, 0.23 mmol) and methylamine (0.24 g, 7.8 mmol). mp 155-157 °C.

Example 405: No compound

Example 406: (±)-[(N-methyl-l-[7-(2-methylphenyl)-2,3-dihydro-l-benzofur an-2- yljniethanamine

The title compound was prepared (0.055g, 24%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-[(7-bromo-2,3-dihydro-l- benzofuran-2-yl)methyl]methylamine (0.20 g, 0.826 mmol) and 2-methylphenylboronic acid (0.168 g, 1.24 mmol). mp 166-169 °C.

Example 407: (-)-N-methyl-l-[7-(2-methylphenyl)-2,3-dihydro-l-benzofuran- 2- yljmethanamine

Treatment of 0.325 g of fraction 1 obtained from the chiral HPLC separation of (±)-benzyl methyl { [7-(2-methylphenyl)-2,3-dihydro- 1 -benzofuran-2-

yl]methyl} carbamate with trimethylsilyl iodide (0.671 g, 3.3 mmol) generally according to the procedure described for Example 158 gave 0.193 g (80%) of (-)-N-methyl-l-[7-(2- methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methanamine as a white solid, hydrochloride salt. [CC] _D = -22.2 (c 10.0 in methanol); mp 182-185 °C.

Example 408: (+)-N-methyl-l-[7-(2-methylphenyl)-2,3-dihydro-l-benzofuran- 2- yl] methanamine

Treatment of 0.32 g of fraction 2 obtained from the chiral HPLC separation of (±)- benzyl methyl{[7-(2-methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]met hyl}carbamate with trimethylsilyl iodide (0.67 g, 3.3 mmol) generally according to the procedure described for Example 158 gave 0.192 g (80%) of (+)-N-methyl-l-[7-(2-methylphenyl)- 2,3-dihydro-l-benzofuran-2-yl]methanamine as a white solid, hydrochloride salt. [α] _D = +26.4 (c 10.0 in methanol); mp 182-185 °C.

Example 409: (±)-[(N-methyl-l-[7-(2-chlorophenyl)-2,3-dihydro-l-benzofur an-2- yl] methanamine

The title compound was prepared (0.078 g, 40%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-[(7-bromo-2,3-dihydro-l- benzofuran-2-yl)methyl]methylamine (0.20 g, 0.826 mmol) and 2-chlorophenylboronic acid (0.194 g, 1.24 mmol). mp 163-165 °C.

Example 410: (+)-N-methyl-l-[7-(2-chlorophenyl)-2,3-dihydro-l-benzofuran- 2- yl] methanamine

Treatment of 2.71 g of fraction 2 obtained from the chiral HPLC separation of (±)- benzyl methyl { [7-(2-chlorophenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methyl } carbamate with trimethylsilyl iodide (5.32 g, 26.57 mmol) generally according to the procedure described for Example 158 gave 1.23 g (60%) of (+)-N-methyl-l-[7-(2-chlorolphenyl)- 2,3-dihydro-l-benzofuran-2-yl]methanamine as a white solid, hydrochloride salt, [α]^ ⁵ = +13.2 (c 10.0 in methanol); mp 154-157 °C.

Example 411: (-)-N-methyl-l-[7-(2-chlorophenyl)-2,3-dihydro-l-benzofuran- 2- yl] methanamine

Treatment of 3.01 g of fraction 1 obtained from the chiral HPLC separation of (±)- benzyl methyl{[7-(2-chlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]met hyl}carbamate with trimethylsilyl iodide (5.91 g, 29.52 mmol) generally according to the procedure described for Example 158 gave 1.80 g (76%) of (+)-N-methyl-l-[7-(2-chlorolphenyl)- 2,3-dihydro-l-benzofuran-2-yl]methanamine as a white solid, hydrochloride salt, [α]^ ⁵ = - 13.2 (c 10.0 in methanol); mp 154-157 ⁰ C.

Example 412: (±)-[(N-methyI-l-[7-(2-fluorophenyl)-2,3-dihydro-l-benzofur an-2- yljmethanamine The title compound was prepared (0.147g, 66%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[7~(2-fluorophenyl)-2,3- dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.300 g, 0.753 mmol) and methylamine (0.92 g, 29.5 mmol). mp 148-150 °C.

Example 413: (±)-[(N-methyl-l-[7-(2-methoxyphenyl)-2,3-dihydro-l-benzofu ran-2- yl]methanamine

The title compound was prepared (0.250 g, 76%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-[7-(2-methoxyphenyl)-2,3- dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.501 g, 1.22 mmol) and methylamine (4.56 g, 150.0 mmol). mp 157-159 °C.

Example 414: (±)-[(N-methyl-l-[7-(3-methylphenyl)-2,3-diliydro-l-benzofu raii-2- yl]methanamine

The title compound was prepared (0.059 g, 26%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-[(7-bromo-2,3-dihydro-l- benzofuran-2-yl)methyl]methylamine (0.200 g, 0.826 mmol) and 3-methylphenylboronic acid (0.169 g, 1.24 mmol). mp 157-159 °C.

Example 415: (±)-[(N-methyl-l-[7-(3-fluorophenyl)-2,3-dihydro-l-benzofur an-2- yljmethanamine

The title compound was prepared (0.38 g, 53%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-[(7-bromo-2,3-dihydro-l-

benzofuran-2-yl)methyl]methylamine (0.200 g, 0.826 mmol) and 3-fluorophenylboronic acid (0.173 g, 1.24 mmol). mp 160-163 °C.

Example 416: (±)-[(N-methyl-l-[7-(3-chlorophenyl)-2,3-dihydro-l-benzofur an-2- yl]methanamine

The title compound was prepared (0.59 g, 53%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-[(7-bromo-2,3-dihydro-l- benzofuran-2-yl)methyl]methylamine (0.200 g, 0.826 mmol) and 3-chlorophenylboronic acid (0.194 g, 1.24 mmol). mp 177-178 °C.

Example 417: (±)-[(N-methyl-l-[7-(3-methoxyphenyI)-2,3-dihydro-l-benzofu ran-2- yl]methanamine

The title compound was prepared (0.41 g, 49%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-[(7-bromo-2,3-dihydro-l- benzofuran-2-yl)methyl]methylamine (0.200 g, 0.826 mmol) and 3- methoxyphenylboronic acid (0.188 g, 1.24 mmol). mp 148-151 °C.

Example 418: (±)-[(N-methyl-l-[7-(4-methylphenyl)-2,3-dihydro-l-benzofur an-2- yl]methanamine The title compound was prepared (0.071 g, 34%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-[(7-bromo-2,3-dihydro-l- benzofuran-2-yl)methyl]methylamine (0.200 g, 0.826 mmol) and 4-methylphenylboronic acid (0.168 g, 1.24 mmol). mp 210-213 °C.

Example 419: (±)-[(N-methyl-l-[7-(4-fluorophenyl)-2,3-dihydro-l-benzofur an-2- yl]methanamine

The title compound was prepared (0.049 g, 21%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-[(7-bromo-2,3-dihydro-l- benzofuran-2-yl)methyl]methylamine (0.200 g, 0.826 mmol) and 4-fluorophenylboronic acid (0.173 g, 1.24 mmol). mp 209-211 °C.

Example 420: (±)-[(N-methyI-l-[7-(4-chlorophenyl)-2,3-dihydro-l-benzofur an-2- yljmethanamine

The title compound was prepared (0.037 g, 16%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-[(7-bromo-2,3-dihydro-l- benzofuran-2-yl)methyl]methylamine (0.200 g, 0.826 mmol) and 4-chlorophenylboronic acid (0.193 g, 1.24 mmol). mp 227-230 ⁰ C.

Example 421: (±)-[(N-methyl-l-[7-(4-methoxyphenyl)-2,3-dihydro-l-benzofu ran-2- yl]methanamine The title compound was prepared (0.052 g, 23%) following the general procedure of Example 154 as a white solid, hydrochloride salt from (±)-[(7-bromo-2,3-dihydro-l- benzofuran-2-yl)methyl]methylamine (0.200 g, 0.826 mmol) and 4- methoxyphenylboronic acid (0.188 g, 1.24 mmol). mp 214-217 ⁰ C.

Example 422: (±)-[(N-methyl-l-[7-(2,3-dimethylphenyl)-2,3-dihydro-l-benz ofuran- 2-yl] methanamine

The title compound was prepared (0.046 g, 65%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[7-(2,3-dimethylphenyl)- 2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.095 g, 0.23 mmol) and methylamine (0.072 g, 2.3 mmol). mp 197-199 °C.

Example 423: (±)-[(N-methyI-l-[7-(2,3-dimethoxyphenyl)-2,3-dihydro-l- benzofuran-2~yl]methanamine

The title compound was prepared (0.137 g, 63%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[7-(2,3-dimethoxyphenyl)- 2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.283 g, 0.64 mmol) and methylamine (0.199 g, 6.42 mmol). mp 163-166 ⁰ C.

Example 424: (±)-[(N-methyl-l-[7-(2,4-difluorophenyl)-2,3-dihydro-l-benz ofuran-2- yl] methanamine

The title compound was prepared (0.137 g, 68%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[7-(2,4-difluorophenyl)-2,3-

dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.366 g, 0.88 mmol) and methylamine (0.273 g, 8.80 mmol). mp 156-160 °C.

Example 425: (±)-[(N-methyl-l-[7-(2,4-dichlorophenyl)-2,3-dihydro-l-benz ofuran- 2-yl]methanamine

The title compound was prepared (0.137 g, 47%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[7-(2,4-dichlorophenyl)-2,3- dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.125 g, 0.278 mmol) and methylamine (0.086 g, 2.78 mmol). mp 190-192 ⁰ C.

Example 426: (±)-[(N-methyl-l-[7-(2,4-dimethoxyphenyl)-2,3-dihydro-l- benzofuran-2-yI]methanamine

The title compound was prepared (0.272 g, 82%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[7-(2,4-dimethoxyphenyl)- 2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.435 g, 0.987 mmol) and methylamine (0.306 g, 9.87 mmol). mp 185-188 ⁰ C.

Example 427: (±)-[(N-methyl-l-[7-(2,5-dimethylphenyl)-2,3-dihydro-l-benz ofuran- 2-yl] methanamine The title compound was prepared (0.091 g, 65%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[7-(2,5-dimethylphenyl)- 2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.091 g, 0.22 mmol) and methylamine (0.069 g, 2.22 mmol). mp 186-189 ⁰ C.

Example 428: (±)-[(N-methyl-l-[7-(2,5-difluorophenyl)-2,3-dihydro-l-benz ofuran-2- yl] methanamine

The title compound was prepared (0.027 g, 60%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[7-(2,5-difluorophenyl)-2,3- dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.060 g, 0.14 mmol) and methylamine (0.045 g, 1.4 mmol). mp 172-174 ⁰ C.

Example 429: (±)-[(N-methyl-l-[7-(2,5-dichlorophenyI)-2,3-dihydro-l-benz ofuran- 2-yI] methanamine

The title compound was prepared (0.068 g, 83%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[7-(2,5-dichlorophenyl)-2,3- dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.120 g, 0.26 mmol) and methylamine (1.24 g, 40.0 mmol). mp 147-149 °C.

Example 430: (±)-[(N-methyl-l-[7-(5-chloro-2-methoxyphenyl)-2,3-dihydro- l- benzofuran-2-yl]methanamine The title compound was prepared(0.058 g, 79%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[7-(5~chloro-2- methoxyphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.095 g, 0.213 mmol) and methylamine (0.045 g, 2.1 mmol). mp 201-203 °C.

Example 431: (±)-[(N-methyl-l-[7-(5-chIoro-2-methylphenyI)-2,3-dihydro-l - benzofuran-2-yl] methanamine

The title compound was prepared (0.051 g, 65%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[7-(5-chloro-2- methylphenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.103 g, 0.24 mmol) and methylamine (0.074 g, 2.4 mmol). mp 178-182 °C.

Example 432: (±)-[(N-methyl-l-[7-(2,6-dimethylphenyl)-2,3-dihydro-l-benz ofuran- 2-yl] methanamine

The title compound was prepared (0.039 g, 63%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[7-(2,6-dimethylphenyl)- 2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.084 g, 0.205 mmol) and methylamine (1.86 g, 60.0 mmol). mp >250 ⁰ C.

Example 433: (±)-[(N-methyl-l-[7-(2,6-dichlorophenyl)-2,3-dihydro-l-benz ofuran- 2-yl] methanamine

The title compound was prepared (0.35 Ig, 77%) following the general procedure of Example 390 as a white solid, hydrochloride salt from [7-(2,6-dichlorophenyl)-2,3-

dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.595 g, 1.324 mmol) and methylamine (1.86 g, 60.0 mmol). 190-192 mp ⁰ C.

Example 434: (-)-{[7-(2,6-dichlorophenyl)-2,3-dihydro-l-benzofuran-2- yl]methyl}methylamine

Treatment of 0.607 g of fraction 1 obtained from the chiral HPLC separation of (±)-benzyl {7-(2,6-dichlorophenyl)-2,3-dihydro-l-benzofuran-2- yl]methyl}methylcarbamate with trimethylsilyl iodide (1.09 g, 5.49 mmol) generally according to the procedure described for Example 158 gave 0.409 g (86%) of (-)-{[7-(2,6- dichlorophenyl)-2,3-dihydrθ ₇ l-benzofuran-2-yl]methyl}methylamine as a white solid, hydrochloride salt, [α]^ ⁵ = -11.6 (c 10.0 in methanol); mp 195-197 ⁰ C.

Example 435: (+)-{[7-(2,6-dichlorophenyl)-2,3-dihydro-l-benzofuran-2- yl]methyl}methylamine Treatment of 0.625 g of fraction 1 obtained from the chiral HPLC separation of

(±)-benzyl {7-(2,6-dichlorophenyl)-2,3-dihydro-l-benzofuran-2- yl] methyl }methylcarbamate with trimethylsilyl iodide (1.131 g, 5.65 mmol) generally according to the procedure described for Example 158 gave 0.369 g (76%) of (+)-{[7- (2,6-dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}me thylamine. [α]^ ⁵ = +11.2 (c 10.0 in methanol); mp 195-197 °C.

Example 436: (±)-N-methyI-l-(7-pyridin-3-yl-2,3-dihydro-l-benzofuran-2- yl)methanamine

The title compound was prepared (0.367g, 70%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (7-pyridin-3-yl-2,3-dihydro-l- benzofuran-2-yl)methyl 4-methylbenzenesulfonate (0.730 g, 1.91 mmol) and methylamine (1.14 g, 36.7 mmol). mp 212-215 °C.

Example 437: (±)-[(N-methyl-l-[7-(2,3-difluorophenyI)-2,3-dihydro-l-benz ofuran-2- yl]methanamine

The title compound was prepared (0.094 g, 84%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[7-(2,3-difluorophenyl)-2,3- dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.095 g, 0.23 mmol) and methylamine (0.072 g, 2.3 mmol); mp 166-168 °C.

Example 438: (±)-{[5-fluoro-7-(2-fluorophenyl)-2,3-dihydro-l-benzofuran- 2- yl)methyl}methylamine The title compound was prepared (0.060 g, 40%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[5~fluoro-7-(2- fluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.2 g, 0.48 mmol) and methylamine (0.149 g, 4.80 mmol). mp 140-141 ⁰ C.

Example 439: (±)-{[5-fluoro-7-(2-chlorophenyl)-2,3-dihydro-l-benzofuran- 2- yl]methyl}methylamine

The title compound was prepared (0.075 g, 52%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[5-fluoro-7-(2- chlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.19 g, 0.44 mmol) and methylamine (0.136 g, 4.40 mmol). mp 141-143.

Example 440: (±)-{[5-fluoro-7-(2-methylphenyl)-2,3-dihydro-l-benzofuran- 2- yl]methyl}methylamine

The title compound was prepared (0.038 g, 34%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[5-fmoro-7-(2- methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.15 g, 0.36 mmol) and methylamine (0.112 g, 3.60 mmol). mp 102-104 °C.

Example 441: (-)-{[5-fluoro-7-(2-methylphenyl)-2,3-dihydro-l-benzofuran-2 - yl]methyl}methylamine

Treatment of 0.22 g of fraction 2 obtained from the chiral HPLC separation of (±)- benzyl { [5-fluoro-7-(2-methylphenyl)-2,3-dihydro- 1 -benzofuran-2-

yl]methyl}methylcarbamate with trimethylsilyl iodide (0.416g, 2.08 mmol) generally according to the procedure described for Example 158 gave 0.125 g (79%) of (-)-{[5- fluoro-7-(2-methylphenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methyl}methylamine as a white solid, hydrochloride salt. [<X] _D = -18.58 (c 10.0 in methanol); mp 123-124 ⁰ C.

Example 442: (+)-{[5-fluoro-7-(2-methylphenyl)-2,3-dihydro-l-benzofuran-2 - yl]methyl}methylamine

Treatment of 0.28 g of fraction 1 obtained from the chiral HPLC separation of (±)- benzyl { [5-fluoro-7-(2-methylphenyl)-2,3-dihydro- 1 -benzofuran-2- yl]methyl}methylcarbarnate with trimethylsilyl iodide (0.528g, 2.64 mmol) generally according to the procedure described for Example 158 gave 0.124 g (61%) of (+)-{[5- fluoro-7-(2-methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]meth yl}methylamine as a white solid, hydrochloride salt, [α]" = +14.25 (c 10.0 in methanol); mp 123-124 °C.

Example 443: (±)-{[5-fluoro-7-(2-methoxyphenyl)-2,3-dihydro-l-benzofuran -2- yl] methyl} methylamine

The title compound was prepared (0.075 g, 37%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[5-fluoro-7-(2- methoxyphenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.27 g, 0.6 mmol) and methylamine (0.198 g, 6.0 mmol). mp 175-176 °C.

Example 444: (±)-{[7-(2,3-dimethoxyphenyl)-5-fluoro-2,3-dihydro-l-benzof uran-2- yl]methyl}methylamine

The title compound was prepared (0.103 g, 74%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[7-(2,3-dimethoxyphenyl)- 5-fluoro-2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.18 g, 0.39 mmol) and methylamine (0.139 g, 3.9 mmol). mp 85-89 °C.

Example 445: (±)-[7-(2,4-dichlorophenyl)-5-fluoro-2,3-dihydro-l-benzofur an-2- yl]methyl}methylamine

The title compound was prepared (0.041 g, 40%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[7-(2,4~dichlorophenyl)-5-

fluoro-2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.13 g, 0.278 mmol) and methylamine (0.086 g, 2.78 mmol). mp 146-148 °C.

Example 446: (-)-[7-(2,4-dichlorophenyl)-5-fluoro-2,3-dihydro-l-benzofura n-2- yl]methyl}methylamine

Treatment of 0.48 g of fraction 2 obtained from the chiral HPLC separation of (±)- benzyl { [7-(2,4-dichlorophenyl)-5-fluoro-2,3-dihydro- 1 -benzofuran-2- yl]methyl}methylcarbamate with trimethylsilyl iodide (0.834 g, 4.17 mmol) generally according to the procedure described for Example 158 gave 0.200 g (53%) of (-)-[7-(2,4- dichlorophenyl)-5-fluoro-2,3-dihydro-l-benzofuran-2-yl]methy l}methylamine as a white solid, hydrochloride salt, [α]" = -8.87 (c 10.0 in methanol); mp 162-163 °C.

Example 447: (+)-[7-(2,4-dichlorophenyl)-5-fluoro-2,3-dihydro-l-benzofura n-2- yl]methyl}methylamme Treatment of 0.48 g of fraction 1 obtained from the chiral HPLC separation of (±)- benzyl {[7-(2,4-dichlorophenyl)-5-fluoro-2,3-dihydro-l-benzofuran-2 - yl]methyl}methylcarbamatewith trimethylsilyl iodide (0.834 g, 4.17 mmol) generally according to the procedure described for Example 158 gave 0.200 g (53%) of (+)-[7-(2,4- dichlorophenyl)-5-fluoro-2,3-dihydro-l-benzofuran-2-yl]methy l}methylamine as a white solid, hydrochloride salt, [άffi = +8.61 (c 10.0 in methanol); mp 161-163 °C.

Example 448: (±)-{[7-(2,5-difluorophenyl)-5-fluoro-2,3-dihydro-l-benzofu ran-2- y 1] methyl} methy lamin e

The title compound was prepared (0.73 g, 44%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[7-(2,5-difluorophenyl)-5- fluoro-2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.22 g, 0.51 mmol) and methylamine (0.155 g, 5.1 mmol). mp 185-187 °C.

Example 449: (±)-{[7-(2,5-dichlorophenyl)-5-fluoro-2,3-dihydro-l-benzofu ran-2- yl]methyl}methylamine

The title compound was prepared. (0.123 g, 80%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[7-(2,5-dichlorophenyl)-5-

fluoro-2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.2 g, 0.43 mmol) and methylamine (0.133 g, 4.3 mmol). mp 166-168 °C.

Example 450: (+)-{[5-fluoro-7-(2,5-dichlorophenyl)-2,3-dihydro-l-benzofur an-2- yl]methyl}methylamine

Treatment of 0.53 g of fraction 1 obtained from the chiral HPLC separation of (±)- benzyl {[7-(2,5-dichlorophenyl)-5-fluoro-2,3-dihydro-l-benzofuran-2 - yl]methyl}methylcarbamate with trimethylsilyl iodide (0.92 g, 4.60 mmol) generally according to the procedure described for Example 158 gave 0.204 g (49%) of (+)-{[5- fluoro-7-(2,5-dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl] methyl}methylamine as a white solid, hydrochloride salt, [α]^ ⁵ = +14.00 (c 10.0 in methanol); mp 118-120 °C.

Example 451: (-)-{[5-fluoro-7-(2,5-dichlorophenyl)-2,3-dihydro-l-benzofur an-2- y 1] methyl} methylamine Treatment of 0.54 g of fraction 2 obtained from the chiral HPLC separation of (±)- benzyl {[7-(2,5-dichlorophenyl)-5-fluoro-2,3-dihydro-l-benzofuran-2 - yl] methyl }methylcarbamate with trimethylsilyl iodide (0.96 g, 4.80 mmol) generally according to the procedure described for Example 158 gave 0.275 g (65%) of (-)-{[5- fluoro-7-(2 _J 5-dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl}methy lamine as a white solid, hydrochloride salt, [α]" = -22.30 (c 10.0 in methanol); mp 110-112 ⁰ C.

Example 452: (±)-{[7-(2,5-dimethylphenyl)-5-fluoro-2,3-dihydro-l-benzofu ran-2- yl]methyl}methylamine

The title compound was prepared (0.76 g, 48%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[7-(2,5-dimethylphenyl)-5- fluoro-2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.21 g, 0.49 mmol) and methylamine (0.152 g, 4.9 mmol). mp 186-188 ⁰ C.

Example 453: (±)-{[7-(2,6-dimethylphenyl)-5-fluoro-2,3-dihydro-l-benzofu ran-2- yl]methyl}methylamme

The title compound was prepared (0.148 g, 65%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[7-(2,6 -dimethylphenyl)-5-

fluoro-2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.3 g, 0.70 mmol) and methylamine (0.22 g, 7.0 mmol). mp 175-178 °C.

Example 454: (±)-{[7-(2,6-dichlorophenyl)-5-fluoro-2,3-dihydro-l-benzofu ran-2- yl]methyl}methylamine

The title compound was prepared (0.081 g, 52%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[7-(2,6 -dichlorophenyl)-5- fluoro-2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.2 g, 0.43 mmol) and methylamine (0.133 g, 4.3 mmol). mp 196-198 °C.

Example 456: (±)-{[5-fluoro-7-(5-methoxy-2-methylphenyl)-2,3-dihydro-l- benzofuran-2-yl]methyl}methylamine

The title compound was prepared (0.73 g, 50%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[5-fluoro-7-(5-methoxy-2- methylphenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.19 g,

0.40 mmol) and methylamine (0.124 g, 4.0 mmol). mp 173-174 °C.

Example 457: (±)-{[5-fluoro-7-(2-methoxy-5-methylphenyl)-2,3-dihydro-l- benzofuran-2-yl]methyl}methylamine The title compound was prepared (0.77 g, 48%)following the general procedure of

Example 390 as a white solid, hydrochloride salt from (±)-[5-fluoro-7-(2-methoxy-5- methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.21 g, 0.45 mmol) and methylamine (0.139 g, 4.5 mmol). mp 197-199 ⁰ C.

Example 458: (±)-{[7-(5-chloro-2-methoxyphenyI)-5-fluoro-2,3-dihydro-l- benzofuran-2-yl] methyl} methylamine

The title compound was prepared (0.62 g, 38%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[7-(5-chloro-2- methoxyphenyl)-5-fluoro-2,3-dihydro- 1 -benzofuran-2-yl]methyl 4- methylbenzenesulfonate (0.21 g, 0.45 mmol) and methylamine (0.139 g, 4.5 mmol). mp 189-190 °C.

Example 459: (±)-[(5-fluoro-7-pyridin-3-yl-2,3-dihydro-l-benzofuran-2- yl)methyl] methylamine

The title compound was prepared (0.056 g, 34%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[5-fluoro-7-pyridin-3-yl-2,3- dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.20 g, 0.50 mmol) and methylamine (0.155 g, 5.0 mmol). mp 255-257 ⁰ C.

Example 460: (±)-[(5-chloro-7-(2-methoxyphenyl)-2,3-dihydro-l-benzofuran -2- yl]methyl}methylamme The title compound was prepared (0.037 g, 29%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[5-chloro-7-(2- methoxyphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.39 g, 0.88 mmol) and methylamine (0.271 g, 8.8 mmol). mp 100-102 ⁰ C.

Example 461: (±)-{[5-chloro-7-(2,6-dimethylphenyl)-2,3-dihydro-l-benzofu ran-2- yl]methyl}methylamine

The title compound was prepared (0.155 g, 62%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[5-chloro-7-(2,6- dimethylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.333 g, 0.74 mmol) and methylamine (0.231 g, 7.4 mmol). mp 229-231 °C.

Example 462: (±)-[(5-chloro-7-(2-fluorophenyl)-2,3-dihydro-l-benzofuran- 2- yl]methyl}methylamine

The title compound was prepared (0.037 g, 34%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[5-chloro-7-(2- fluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.142 g, 0.33 mmol) and methylamine (0.102 g, 3.3 mmol). mp 159-161 °C.

Example 463: (±)-{[5-chloro-7-(2,3-difluorophenyl)-2,3-dihydro-l-benzofu ran-2- yl]methyl}methylamine

The title compound was prepared (0.068 g, 60%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[5-chloro-7-(2,3-

difluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.148 g, 0.329 mmol) and methylamine (0.102 g, 3.29 mmol). mp 177-179 °C.

Example 464: (±)-{[5-chloro-7-(2,3-dichlorophenyl)-2,3-dihydro-l-benzofu ran-2- yl]methyl}methylamine

The title compound was prepared (0.051 g, 40%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[5-chloro-7-(2,3- dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.165 g, 0.341 mmol) and methylamine (0.106 g, 3.41 mmol). mp 219-221 °C.

Example 465: (±)-{[5-chloro-7-(2,3-dimethylphenyl)-2,3-dihydro-l-benzofu ran-2- y 1] methyl} methylamine

The title compound was prepared (0.054 g, 47%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[5-chloro-7-(2,3- dimethylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.149 g, 0.33 mmol) and methylamine (0.102 g, 3.3 mmol). mp 148-150 °C.

Example 466: (±)-{[5-chloro-7-(2,3-dimethoxyphenyl)-2,3-dihydro-l-benzof uran-2- yl]methyl}methylamme The title compound was prepared (0.046 g, 34%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[5-chloro-7-(2,3- dimethoxyphenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.172 g, 0.36 mmol) and methylamine (0.112 g, 3.6 mmol). mp 105-107 °C.

Example 467: (±)-{[5-chloro-7-(2,4-difluorophenyl)-2,3-dihydro-l-benzofu ran-2- yl]methyl}methylamine

The title compound was prepared (0.059 g, 48%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[5-chloro-7-(2,4- difluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.162 g, 0.36 mmol) and methylamine (0.112 g, 3.6 mmol). mp 163-165 °C.

Example 468: (±)-{[5-chloro-7-(2,4-dichlorophenyl)-2,3-dihydro-l-benzofu ran-2- yl]methyl}methylamine

The title compound was prepared (0.059 g, 57%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[5-chloro-7-(2,4- dichlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.135 g, 0.28 mmol) and methylamine (0.086 g, 2.8 mmol). mp 202-204 °C.

Example 469: (±)-{[5-chloro-7-(2,4-dimethoxyphenyl)-2,3-dihydro-l-benzof uran-2- yl]methyl}methylamine The title compound was prepared (0.052 g, 68%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[5-chloro-7-(2,4- dimethoxyphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.099 g, 0.21 mmol) and methylamine (0.065 g, 2.1 mmol). mp 206-208 °C.

Example 470: (±)-{[S-chloro-7-(2,5-difluorophenyl)-2,3-dihydro-l-benzofu ran-2- yl]methyl}methylamine

The title compound was prepared (0.090 g, 67%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[5~chloro-7~(2,5- difluorophenyl)-2,3-dihydro- 1 -benzofuran-2-yl] methyl 4-methylbenzenesulfonate (0.175 g, 0.39 mmol) and methylamine (0.120 g, 3.9 mmol). mp 189-191 °C.

Example 471: (±)-{[5-chloro-7-(2,5-dichlorophenyl)-2,3-dihydro-l-beiizof uraii-2- y 1] methyl} methylamine

The title compound was prepared (0.027 g, 23%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[5-chloro-7-(2,5- dichlorophenyl)-2,3-dihydro-l -benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.152 g, 0.31 mmol) and methylamine (0.086 g, 3.1 mmol). mp 185-187 °C.

Example 472: (±)-{[5-chIoro-7-(5-chloro-2-methoxyphenyl)-2,3-dihydro-l- benzofuran-2-yl]methyl}methylamine

The title compound was prepared (0.027 g, 21%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[5-chloro-7-(5-chloro-2-

methoxyphenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.165 g, 0.34 mmol) and methylamine (0.107 g, 3.4 mmol). mp 193-195 °C.

Example 473: (±)-{[5-chloro-7-(3.4-difluorophenyl)-2,3-dihydro-l-benzofu ran-2- yl]methyl}methylamine

The title compound was prepared (0.09 g, 79%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[5-chloro-7-(3,4- difluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.149 g, 0.33 mmol) and methylamine (0.102 g, 3.3 mmol). mp 235-237 °C.

Example 474: (±)-[5-chloro-7-(3-chloro-4-fluorophenyl)-2,3-dihydro-l-ben zofuran- 2-yl]methyl}methylamine

The title compound was prepared (0.032 g, 48%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[5-chloro-7-(3-chloro-4- fluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.086 g, 0.18 mmol) and methylamine (0.057 g, 1.8 mmol). mp 202-204 °C.

Example 475: (±)-{[7-(2-fluorophenyl)-5-methyl-2,3-dihydro-l-benzofuran- 2- yl]methyl}methylamine The title compound was prepared (0.03 g, 28%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[7-(2-fluorophenyl) 5- methyl-2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.14 g, 0.34 mmol) and methylamine (0.105 g, 3.4 mmol). mp 153-155 °C.

Example 476: (±)-{[7-(2-chlorophenyl)-5-methyl-2,3-dihydro-l-benzofuran- 2- yl]methyl}methylamine

The title compound was prepared (0.060 g, 28%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[7-(2-chlorophenyl) 5- methyl-2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.22 g, 0.50 mmol) and methylamine (0.155 g, 5.0 mmol). mp 194-196 ⁰ C.

Example 477: (±)-{[7-(2-methoxyphenyl)-5-methyl-2,3-dihydro-l-benzofuran -2- yl]methyl}methylamine

The title compound was prepared (0.041 g, 32%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[7-(2-methoxyphenyl) 5- methyl-2,3-dihydro- 1 -benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.17 g, 0.40 mmol) and methylamine (0.124 g, 4.0 mmol). mp 165-166 °C.

Example 478: (±)-{[7-(3-methylphenyl)-5-methyl-2,3-dihydro-l-benzofuran- 2- yl]methyl}methylamine The title compound was prepared (0.075 g, 60%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[7-(3-methylphenyl) 5- methyl-2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.17 g, 0.42 mmol) and methylamine (0.129 g, 4.2 mmol). mp 165-167 °C.

Example 479: (±)-{[7-(3-chlorophenyl)-5-methyl-2,3-dihydro-l-benzofuran- 2- yl] methyl} methylamine

The title compound was prepared (0.016 g, 13%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[7-(3-chlorophenyl) 5- methyl-2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.16 g, 0.37 mmol) and methylamine (0.115 g, 3.7 mmol). mp 181-182 °C.

Example 480: (±)-{[7-(4-methylphenyl)-5-methyl-2,3-dihydro-l-benzofuran- 2- yl]methyl}methylamine

The title compound was prepared (0.049 g, 44%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[7-(4-methylphenyl) 5- methyl-2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.15 g, 0.37 mmol) and methylamine (0.114 g, 3.7 mmol). mp 184-185 °C.

Example 481: (±)-{[7-(4-chIorophenyl)-5-methyl-2,3-dihydro-l-benzofuran- 2- yl] methyl} methylamine

The title compound was prepared (0.026 g, 21%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[7-(4-chlorophenyl) 5-

methyl-2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.16 g, 0.37 mmol) and methylamine (0.115 g, 3.7 mmol). mp 210-213 °C.

Example 482: (±)-{[7-(4-fluorophenyl)-5-methyI-2,3-dihydro-l-benzofuran- 2- yl]methyl}methylamine

The title compound was prepared (0.028 g, 25%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[7-(4-fluorophenyl) 5- methyl-2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.15 g, 0.36 mmol) and methylamine (0.112 g, 3.6 mmol). mp 206-208 °C.

Example 483: (±)-{[7-(4-methoxyphenyl)-5-methyl-2,3-dihydro-l-benzofuran -2- yl]methyl}methylamine

The title compound was prepared (0.075 g, 52%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[7-(4-methoxyphenyl) 5- methyl-2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.19 g, 0. 45 mmol) and methylamine (0.112 g, 4.5 mmol). mp 235-238 °C.

Example 484: (±)-{[7-(2,3-dimethoxyphenyl)-5-methyl-2,3-dihydro-l-benzof uran-2- yl] methyl} methylamine The title compound was prepared (0.094 g, 44%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[7-(2,3-dimethoxyphenyl) 5- methyl-2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.18 g, 0.40 mmol) and methylamine (0.123 g, 4.0 mmol). mp 85-89 °C.

Example 485: (±)-{[7-(2,4-dichlorophenyl)-5-methyl-2,3-dihydro-l-benzofu ran-2- yl]methyl}methylamine

The title compound was prepared (0.029 g, 14%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[7-(2,4-dichlorophenyl) 5- methyl-2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.26 g, 0.56 mmol) and methylamine (0.174 g, 5.6 mmol). mp 169-171 °C.

Example 486: (±)-{[7-(2,5-dichlorophenyl)-5-methyl-2,3-dihydro-l-benzofu ran-2- yl]methyl}methylamine

The title compound was prepared (0.034 g, 27%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[7-(2,5-dichlorophenyl) 5- methyl-2,3-dihydro~ 1 -benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.16 g, 0.34 mmol) and methylamine (0.107 g, 3.4 mmol). nip 158-160 °C.

Example 487: (+)-{[7-(2,5-dichlorophenyl)-5-methyl-2,3-dihydro-l-benzofur an-2- yl]methyl}methylamine Treatment of 0.51 g of fraction 1 obtained from the chiral HPLC separation of (±)- benzyl { [7-(2,5-dichlorophenyl)-5-methyl-2,3-dihydro- 1 -benzofuran-2- yl]methyl}methylcarbamate with trimethylsilyl iodide (0.88 g, 4.4 mmol) generally according to the procedure described for Example 158 gave 0.256 g (64%) of (+)-{[7- (2,5-dichlorophenyl)-5-methyl-2,3-dihydro- 1 -benzofuran-2-yl]methyl}methylamine as a white solid, hydrochloride salt, [α]" = +14.0 (c 10.0 in methanol); mp 192-194 °C.

Example 488: (-)-{[7-(2,5-dichlorophenyl)-5-methyl-2,3-dihydro-l-benzofur an-2- yl]methyl}methylamine

Treatment of 0.50 g of fraction 2 obtained from the chiral HPLC separation of (±)- benzyl { [7-(2,5-dichlorophenyl)-5-methyl-2,3-dihydro- 1 -benzofuran-2- yl] methyl }methylcarbamate with trimethylsilyl iodide (0.88 g, 4.4 mmol) generally according to the procedure described for Example 158 gave 0.132 g (33%) of (-)-{[7-(2,5- dichlorophenyl)-5-methyl-2,3-dihydro-l-benzofuran-2-yl]methy l}methylamine as a white solid, hydrochloride salt, [α]" = -12.99 (c 10.0 in methanol); mp 192-194 °C.

Example 489: (±)-{[7-(2,6-dimethylphenyl)-5-methyl-2,3-dihydro-l-benzofu ran-2- yl]methyl}methylamine

The title compound was prepared (0.035 g, 46%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[7-(2,6-dimethylphenyl) 5- methyl-2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.10 g, 0.24 mmol) and methylamine (0.073 g, 2.4 mmol). mp 204-205 ⁰ C.

Example 490: (±)-{[7-(2,6-dichlorophenyl)-5-methyl-2,3-dihydro-l-benzofu ran-2- yl]methyl}methylamine

The title compound was prepared (0.073 g, 78%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[7-(2,6-dichlorophenyl) 5- methyl-2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.12 g, 0.26 mmol) and methylamine (0.080 g, 2.6 mmol). mp 192-195 °C.

Example 491: (±)-{[7-(2-fluorophenyl)-5-methoxy-2,3-dihydro-l-benzofuran -2- yl]methyl}methylamine The title compound was prepared (0.039 g, 51 %) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-{[7-(2-fluorophenyl)-5- methoxy-2,3-dihydro-l-benzofuran-2-yl]methyl}4-methylbenzene sulfonate (0.102 g, 0.24 mmol) and methylamine (0.074 g, 2.4 mmol). mp 110-112 ⁰ C.

Example 492: (±)-{[7-(2-chlorophenyl)-5-methoxy-2,3-dihydro-l-benzofuran -2- yl]methyl}methylamine

The title compound was prepared (0.040 g, 52%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-{[7-(2-chlorophenyl)-5- methoxy-2,3-dihydro-l-benzofuran-2-yl]methyl}4-methylbenzene sulfonate (0.102 g, 0.23 mmol) and methylamine (0.071 g, 2.3 mmol). mp 185-186 ⁰ C.

Example 493: (±)-{[7-(2~methylphenyl)-5-methoxy-2,3-dihydro-l-benzofuran -2- yl] methyl} methylamine

The title compound was prepared (0.055 g, 54%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-{[7-(2-methylphenyl)-5- methoxy-2,3-dihydro-l-benzofuran-2-yl]methyl}4-methylbenzene sulfonate (0.135 g, 0.32 mmol) and methylamine (0.099 g, 3.2 mmol). mp 167-169 °C.

Example 494: (±)-{[7-(2,3-difluorophenyl)-5-methoxy-2,3-dihydro-l-benzof uran-2- yl]methyl}methylamine

The title compound was prepared (0.017 g, 18%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-{[7-(2,3-difiuorophenyl)-5-

methoxy-2,3-dihydro-l-benzofuran-2-yl]methyl}4-methylbenzene sulfonate (0.12 g, 0.27 mmol) and methylamine (0.082 g, 2.7 mmol). mp 148-150 ⁰ C.

Example 495: (±)-{[7-(2,3-dichlorophenyl)-5-methoxy-2,3-dihydro-l-benzof uran-2- yl]methyl}methylamine

The title compound was prepared (0.053 g, 68%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-{[7-(2,3-dichlorophenyl)-5- methoxy-2,3-dihydro-l-benzofuran-2-yl]methyl}4-methylbenzene sulfonate (0.135 g, 0.28 mmol) and methylamine (0.087 g, 2.8 mmol). mp 178-180 °C.

Example 496: (±)-{[7-(2,3-dimethylphenyl)-5-methoxy-2,3-dihydro~l~benzof uran-2- yl]methyl}methylamine

The title compound was prepared (0.064 g, 64%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-{[7-(2,3-dimethylphenyi)-5- methoxy-2,3-dihydro-l-benzofuran-2-yl]methyl}4-methylbenzene sulfonate (0.132 g, 0.30 mmol) and methylamine (0.093 g, 3.0 mmol). mp 177-179 ⁰ C.

Example 497: (±)-{[7-(2,4-difluorophenyl)-5-methoxy-2,3-dihydro-l-benzof uran-2- yl]methyl}methylamine The title compound was prepared (0.062 g, 61%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-{[7-(2,4-difluorophenyl)-5- methoxy-2,3-dihydro-l-benzofuran-2-yl]methyl}4-methylbenzene sulfonate (0.132 g, 0.29 mmol) and methylamine (0.092 g, 2.9 mmol). mp 179-181 °C.

Example 498: (±)-{[7-(2,5-difluorophenyl)-5-methoxy-2,3-dihydro-l-benzof uran-2- yl]methyl}methylamme

The title compound was prepared (0.027 g, 27%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-{[7-(2,5-difluorophenyl)-5- methoxy-2 ₅ 3-dihydro-l-benzofuran-2-yl]methyl}4-methylbenzenesulfonate (0.129 g, 0.29 mmol) and methylamine (0.090 g, 2.9 mmol). mp 163-165 °C.

Example 499: (±)-{[7-(2,5-dichlorophenyl)-5-methoxy-2,3-dihydro-l-benzof uran-2- yl]methyl}methylamine

The title compound was prepared (0.061 g, 56%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-{[7-(2,5-dichlorophenyl)-5- methoxy-2,3-dihydro-l-benzofuran-2-yl]methyl}4-methylbenzene sulfonate (0.139 g, 0.29 mmol) and methylamine (0.090 g, 2.9 mmol). mp 179-181 °C.

Example 500: (±)-{[7-(2,5-dimethylphenyl)-5-methoxy-2,3-dihydro-l-benzof uran-2- yl]methyl}methylamine The title compound was prepared (0.064 g, 62%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-{[7-(2,5-dimethylphenyl)-5- methoxy-2,3-dihydro-l-benzofuran-2-yl]methyl}4-methylbenzene sulfonate (0.135 g, 0.31 mmol) and methylamine (0.096 g, 3.1 mmol). mp 202-204 °C.

Example 501: (±)-{[7-(2,5-dimethoxyphenyl)-5-methoxy-2,3-dihydro-l-benzo furan- 2-yl]methyl}methylamine

The title compound was prepared (0.032 g, 27%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-{[7-(2,5-dimethoxyphenyl)- 5-methoxy-2,3-dihydro-l-benzofuran-2-yl]methyl}4-methylbenze nesulfonate (0.152 g, 0.32 mmol) and methylamine (0.100 g, 3.2 mmol). mp 144-145 ⁰ C.

Example 502: (±)-{[7-(5-chloro-2-methoxyphenyl)-5-methoxy-2,3-dihydro-l- benzofuran-2-yl]methyI}methylamme

The title compound was prepared (0.067 g, 58%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-{[7-(5-chloro-2- methoxyphenyl)-5-methoxy-2,3-dihydro-l-benzofuran-2-yl]methy l}4- methylbenzenesulfonate (0.148 g, 0.31 mmol) and methylamine (0.097 g, 3.1 mmol). mp 169-171 °C.

Example 503: (±)-{[7-(3-chloro-4-fluorophenyl)-5-methoxy-2,3-dihydro-l- benzofuran-2-yl]methyl}methylamine

The title compound was prepared (0.052 g, 46%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-{[7-(3-chloro-4- fluorophenyl)-5-methoxy-2,3-dihydro-l-benzofuran-2-yl]methyl }4- methylbenzenesulfonate (0.14 g, 0.31 mmol) and methylamine (0.097 g, 3.1 mmol). mp 197-199 ⁰ C.

Example 504: (±)-{[7-(2,6-dimethyIphenyl)-5-methoxy-2,3-dihydro-l-benzof uran-2- y 1] methyl} methylamine

The title compound was prepared (0.076 g, 57%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-{[7-(2,6-dimethylphenyl)-5- methoxy-2,3-dihydro-l-benzofuran-2-yl]methyl}4-methylbenzene sulfonate (0.175 g, 0.40 mmol) and methylamine (0.12 g, 4.0 mmol). mp 170-172 ⁰ C.

Example 505: (±)-{[7-(2-chlorophenyl)-5-phenyl-2,3-dihydro-l-benzofuran- 2- yl]methyl}methylamine

The title compound was prepared (0.066 g, 84%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-{[7-(2-chlorophenyl)-5- phenyl-2,3-dihydro-l-benzofuran-2-yl]methyl}4-methylbenzenes ulfonate (0.10 g, 0.20 mmol) and methylamine (0.30 g, 9.8 mmol). 192-194 mp °C.

Example 506: (±)-{[7-(3-chlorophenyl)-5-phenyl-2,3-dihydro-l-benzofuran- 2- yl] methyl} methylamine

The title compound was prepared (0.055 g, 69%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-{[7-(3-chlorophenyl)-5- phenyl-2,3-dihydro-l-benzofuran-2-yl]methyl}4-methylbenzenes ulfonate (0.10 g, 0.20 mmol) and methylamine (0.30 g, 9.8 mmol). mp 211-214 ⁰ C.

Example 507: (±)-{[7-(4-chlorophenyl)-5-phenyl-2,3-dihydro-l-benzofuran- 2- yl]methyl}methylamine The title compound was prepared (0.056 g, 71%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-{[7~(4-chlorophenyl)-5-

phenyl-2,3-dihydro-l-benzofuran-2-yl]methyl}4-methylbenzenes ulfonate (0.10 g, 0.20 mmol) and methylamine (0.30 g, 9.8 mmol). mp >250 ⁰ C.

Example 508: (±)-{[7-(2-fluorophenyI)-5-phenyl-2,3-dihydro-l-benzofuran- 2- yl]methyl}methylamine

The title compound was prepared (0.065 g, 83%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-{[7-(2-fluorophenyl)-5- phenyl-2,3-dihydro-l-benzofuran-2-yl]methyl}4-methylbenzenes ulfonate (0.10 g, 0.21 mmol) and methylamine (0.30 g, 9.8 mmol). mp 204-206 °C.

Example 509: (±)-{[7-(3-fluorophenyl)-5-phenyl-2,3-dihydro-l-benzofuran- 2- yl]methyl}methylamine

The title compound was prepared (0.058 g, 74%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-{[7-(3-fluorophenyl)-5- phenyl-2,3-dihydro-l-benzofuran-2-yl]methyl}4-methylbenzenes ulfonate (0.10 g, 0.21 mmol) and methylamine (0.30 g, 9.8 mmol). mp >250 °C.

Example 510: (±)-{[7-(4-fluorophenyl)-5-phenyl-2,3-dihydro-l-benzofuran- 2- yl]methyl}methylamine The title compound was prepared (0.040 g, 51%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-{[7-(4-fluorophenyl)-5- phenyl-2,3-dihydro-l-benzofuran-2-yl]methyl}4-methylbenzenes ulfonate (0.10 g, 0.21 mmol) and methylamine (0.30 g, 9.8 mmol). mp >250 ⁰ C.

Example 511: (±)-{[7-(2-methyIphenyI)-5-phenyl-2,3-dihydro-l-benzofuran- 2- yl]methyl}methylamine

The title compound was prepared (0.055 g, 70%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-{[7-(2-methylphenyl)-5- phenyl-2,3-dihydro-l-benzofuran-2-yl]methyl}4-methylbenzenes ulfonate (0.10 g, 0.21 mmol) and methylamine (0.30 g, 9.8 mmol). mp 232-235 °C.

Example 512: (±)-{[7-(3-methylphenyI)-5-phenyl-2,3-dihydro-l-benzofuran- 2- yl]methyl}methylamine

The title compound was prepared (0.055 g, 70%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-{[7-(3-methylphenyl)-5- phenyl-2,3-dihydro-l-benzofuran-2-yl]methyl}4-methylbenzenes ulfonate (0.10 g, 0.21 mmol) and methylamine (0.30 g, 9.8 mmol). mp 230-234 °C.

Example 513: (±)-{[7-(4-methylphenyl)-5-phenyl-2,3-dihydro-l-benzofuran- 2- yl]methyl}methylamme The title compound was prepared (0.051 g, 65%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-{[7-(4-methylphenyl)-5- phenyl-2,3-dihydro-l-benzofuran-2-yl]methyl}4-methylbenzenes ulfonate (0.10 g, 0.213 mmol) and methylamine (0.30 g, 9.8 mmol). mp >250 ⁰ C.

Example 514: (±)-{[7-(2-methoxyphenyI)-5-phenyl-2,3-dihydro-l-benzofuran -2- yl]methyl}methylamine

The title compound was prepared (0.060 g, 76%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-{[7-(2-methoxyphenyl)-5- phenyl-2, 3 -dihydro-l-benzofuran-2-yl] methyl }4-methylbenzenesulfonate (0.10 g, 0.21 mmol) and methylamine (0.30 g, 9.8 mmol). mp 140-143 ⁰ C.

Example 515: (±)-{[7-(3-methoxyphenyl)-5-phenyl-2,3-dihydro-l-benzofuran -2- yl]methyl}methylamine

The title compound was prepared (0.053 g, 67%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-{[7-(3-methoxyphenyl)-5- phenyl-2,3-dihydro-l-benzofuran-2-yl]methyl}4-methylbenzenes ulfonate (0.10 g, 0.21 mmol) and methylamine (0.30 g, 9.8 mmol). mp 206-209 °C.

Example 516: (±)-{[7-(4-methoxyphenyl)-5-phenyl-2,3-dihydro-l-benzofuran -2- yl]methyl}methylamine

The title compound was prepared (0.081 g, 99%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-{[7-(4-methoxyphenyl)-5-

phenyl-2,3-dihydro-l-benzofuran-2-yl]methyl}4-methylbenze nesulfonate (0.10 g, 0.21 mmol) and methylamine (0.30 g, 9.8 mmol). mp >250 °C.

Example 517: (±)-{[7-(2,4-difluorophenyl)-5-phenyI-2,3-dihydro-l-benzofu ran-2- yl]methyl}methylamine

The title compound was prepared (0.047 g, 59%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-{[7-(2,4-difluorophenyl)-5- phenyl-2,3-dihydro-l-benzofuran-2-yl]methyl}4-methylbenzenes ulfonate (0.10 g, 0.20 mmol) and methylamine (0.30 g, 9.8 mmol). mp 188-191 °C.

Example 518: (±)-{[N-methyl-l-[7-phenyl-5-(trifluoromethyl)-2,3-dihydro- l- benzofuran-2-yl]methanamine

The title compound was prepared (0.031 g, 67%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[7-phenyl-5- (trifluoromethyl)-2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate

(0.060 g, 0.13 mmol) and methylamine (0.12 g, 3.9 mmol). mp 189-190 °C.

Example 519: (±)-N-methyl-l-[7-(3-methylphenyl)-5-(trifluoromethyl)-2,3- dihydro- l-benzofuran-2-yl]methanamine The title compound was prepared (0.026 g, 67%) following the general procedure of Example 390 as a white solid, hydrochloride salt from [7-(3-methylphenyl)-5- (trifluoromethyl)-2,3-dihydro- 1 -benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.050 g, 0.1 lmmol) and methylamine (0.12 g, 3.9 mmol). mp 228-230 °C.

Example 520: (±)-N-methyl-l-[7-(3-fluorophenyl)-5-(trifluoromethyl)-2,3- dihydro- l-benzofuran-2-yl]methanamme

The title compound was prepared (0.026 g, 60%) following the general procedure of Example 390 as a white solid, hydrochloride salt from [7-(3-fluorophenyl)-5- (trifluoromethyl)-2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.055 g, 0.18 mmol) and methylamine (0.12 g, 3.9 mmol). mp 238-240 °C.

Example 521: (±)-N-methyl-l-[7-(2,3-difluorophenyI)-5-(trifluoromethyl)- 2,3- dihydro-l-benzofuran-2-yl]methanamine

The title compound was prepared (0.015 g, 19%) following the general procedure of Example 390 as a white solid, hydrochloride salt from [7-(2,3-difiuorophenyl)-5- (trifluoromethyl)-2,3-dihydro-l -benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.10 g, 0.21 mmol) and methylamine (0.12 g, 3.9 mmol). mp 123-125 °C.

Example 522: (±)-N-methyl-l-[7-(3,4-difluorophenyl)-5-(trifluoromethyl)- 2,3- dihydro-l-benzofuran-2~yl]methanamme The title compound was prepared (0.035 g, 48%) following the general procedure of Example 390 as a white solid, hydrochloride salt from [7-(3,4-difluorophenyl)-5- (trifluoromethyl)-2,3-dihydro- 1 -benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.093 g, 0.19 mmol) and methylamine (0.12 g, 3.9 mmol). mp 235-237 °C.

Example 523: (±)-N-methyl-l-[7-(2,5~difluorophenyl)-5-(trifluoromethyl)- 2,3- dihydro-l-benzofuran-2-yI]methanamme

The title compound was prepared (0.045 g, 58%) following the general procedure of Example 390 as a white solid, hydrochloride salt from [7-(2,5-difluorophenyl)-5- (trifluoromethyl)-2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.10 g, 0.21 mmol) and methylamine (0.12 g, 3.9 mmol). mp 138-140 °C.

Example 524: (±)-N-methyl-l-[7-(2,3-dichlorophenyl)-5-(trifluoromethyl)- 2,3- dihydro-l-benzofuran-2-yl]methanamme

The title compound was prepared f(0.039 g, 49%) ollowing the general procedure of Example 390 as a white solid, hydrochloride salt from [7-(2,3-dichlorophenyl)-5-

(trifluoromethyl)-2,3-dihydro- 1 -benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.10 g, 0.19 mmol) and methylamine (0.12 g, 3.9 mmol). mp 238-240 °C.

Example 525: (±)-{[7-(3-chloro-4-fluorophenyl)-5-(trifluoromethyl)-2,3-d ihydro-l- benzofuran-2-yl]methyl}methylamine

The title compound was prepared (0.014 g, 19%) following the general procedure of Example 390 as a white solid, hydrochloride salt from [7-(3-chloro-4-fiuorophenyl)-5-

(trifluoromethyl)-2,3-dihydro- 1 -benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.095 g, 0.19 mmol) and methylamine (0.12 g, 3.9 mmol). mp 229-230 ⁰ C.

Example 526: (±)-N-methyl-l-[7-(2,4-dimethoxyphenyl)-5-(trifluoromethyl) -2,3- dihydro-l-benzofuran-2-yI]methanamine

The title compound was prepared (0.048 g, 76%) following the general procedure of Example 390 as a white solid, hydrochloride salt from [7-(2,4-dimethoxyρhenyl)-5- (trifluoromethyl)-2,3-dihydro- 1 -benzofuran-2-yl] methyl 4-methylbenzenesulfonate (0.080 g, 0.16 mmol) and methylamine (0.12 g, 3.9 mmol). mp 234-236 °C.

Example 527: (±)-{[7-[3,5-bis(trifluoromethyI)phenyl]-5-(trifluoromethyl )-2,3- dmydro-l-benzofuran-2-yl]methyl}methylamine

The title compound was prepared (0.033 g, 58%) following the general procedure of Example 390 as a white solid, hydrochloride salt from [7-[3,5- bis(trifluoromethyl)phenyl]-5-(trifluoromethyl)-2,3-dihydro- l-benzofuran-2-yl]methyl 4- methylbenzenesulfonate (0.070 g, 0.12 mmol) and methylamine (0.12 g, 3.9 mmol). mp 205-207 °C.

Example 528: (±)-{[7-fluoro-5-(2-methyIphenyl)-2,3-dihydro-l-benzofuran- 2- yl]methyl}methylamine

The title compound was prepared (0.075 g, 75%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[7-fluoro-5-(2- methylphenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.141 g, 0.32 mmol) and methylamine (0.20 g, 6.4 mmol). mp 212-217 ⁰ C (dec).

Example 529: (±)-{[7-fluoro-5-(2-chlorophenyl)-2,3-dihydro-l-benzofuran- 2- yl]methyl}methylamine

The title compound was prepared (0.068 g, 47%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[7-fluoro-5-(2- chlorophenyl)-2 ₅ 3-dihydro-l -benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.199 g, 0.46 mmol) and methylamine (0.28 g, 9.2 mmol). mp 217-222 ⁰ C (dec).

Example 530: (±)-{[7-fluoro-5-(2-fluorophenyl)-2,3-dihydro-l-benzofuran- 2- yl]methyl}methylamine

The title compound was prepared (0.132 g, 92%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[7-fluoro-5-(2- fluorophenyl)-2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.20 g, 0.48 mmol) and methylamine (0.30 g, 9.6 mmol). mp >250 °C (dec).

Example 531 : (±)-{7-fluoro-5-[2-(trifluoromethyl)phenyl]-2,3-dihydro-l- benzofuran-2-yl}methyl)methylamine The title compound was prepared (0.02 g, 18%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[{7-fluoro-5-[2- (trifluoromethyl)phenyl]-2,3-dihydro-l-benzofuran-2-yl}methy l 4- methylbenzenesulfonate (0.21 g, 0.45 mmol) and methylamine (0.28 g, 9.0 mmol). mp 196-200 °C (dec).

Example 532: (±)-{7-fluoro-5-[2-methoxyphenyl]-2,3-dihydro-l-benzofuran- 2- yl}methyl)methylamine

The title compound was prepared (0.13 g, 92%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[{7-fluoro-5-[2- methoxyphenyl]-2,3-dihydro-l-benzofuran-2-yl}methyl 4-methylbenzenesulfonate (0.18 g, 0.42 mmol) and methylamine (0.26 g, 8.4 mmol). mp 223-226 °C (dec).

Example 533: (±)-{7-fluoro-5-[3-methylphenyl]-2,3-dihydro-l-benzofuran-2 - yl}methyl)methylamine The title compound was prepared (0.14 g, 99%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[{7-fluoro-5-[3- methylphenyl]-2,3-dihydro-l-benzofuran-2-yl}methyl 4-methylbenzenesulfonate (0.20 g, 0.48 mmol) and methylamine (0.30 g, 9.6 mmol). mp 245-250 ⁰ C.

Example 534: (±)-{7-fluoro-5-[3-chlorophenyI]-2,3-dihydro-l-benzofuran-2 - yl}methyl)methylamine

The title compound was prepared (0.11 g, 81%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[{7-fluoro-5-[3- chlorophenyl]-2,3-dihydro-l-benzofuran-2-yl}methyl 4-methylbenzenesulfonate (0.21 g, 0.49 mmol) and methylamine (0.30 g, 9.6 mmol). mp 225-232 ⁰ C.

Example 535: (±)-{[7-fluoro-5-(3-fluorophenyl)-2,3-dihydro-l-benzofuran- 2- yl]methyl}methylamine

The title compound was prepared (0.12 g, 88%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[7-fluoro-5-(3- fluorophenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.19 g, 0.45 mmol) and methylamine (0.28 g, 9.1 mmol). mp >250 ⁰ C.

Example 536: (±)-{7-fluoro-5-[3-(trifluoromethyl)phenyl]-2,3-dihydro-l- benzofuran-2-yl}methyl)methylamine The title compound was prepared (0.034 g, 23%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[{7-fluoro-5-[3- (trifluoromethyl)phenyl]-2,3-dihydro- 1 -benzofuran-2-yl}methyl 4- methylbenzenesulfonate (0.19 g, 0.42 mmol) and methylamine (0.26 g, 8.5 mmol). mp 215-219 °C.

Example 537: (±)-{7-fluoro-5-[3-methoxyphenyl]-2,3-dihydro-l-benzofuran- 2- yl}methyl)methylamine

The title compound was prepared (0.13 g, 99%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[{7-fluoro-5-[3- methoxyphenyl]-2,3-dihydro-l-benzofuran-2-yl}methyl 4-methylbenzenesulfonate (0.18 g, 0.42 mmol) and methylamine (0.26 g, 8.3 mmol). mp 214-217 ⁰ C.

Example 538: (±)-{7-fluoro-5-[4-methylphenyl]-2,3-dihydro-l-benzofuran-2 - yl}methyl)methylamine The title compound was prepared (0. H g, 88%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[{7-fluoro-5-[4-

methylphenyl]-2,3-dihydro-l-benzofuran-2-yl}methyl 4-methylbenzenesulfonate (0.17 g, 0.41 mmol) and methylamine (0.26 g, 8.3 mmol). mp >250 °C.

Example 539: (±)-{7-fluoro-5-[4-chlorophenyl]-2,3-dihydro-l-benzofuran-2 - yl}methyl)methylamine

The title compound was prepared (0.14 g, 91%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[{7-fluoro-5-[4- chlorophenyl]-2,3-dihydro-l-benzofuran-2-yl}methyl 4-methylbenzenesulfonate (0.21 g, 0.49 mmol) and methylamine (0.30 g, 9.8 mmol). mp >250 °C.

Example 540: (±)-{[7-fluoro-5-(4-fluorophenyl)-2,3-dihydro-l-benzofuran- 2- yl]methyl}methylamine

The title compound was prepared (0.12 g, 96%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[7-fluoro-5-(4- fluorophenyl)-2,3-dihydro- 1 -benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.18 g, 0.43 mmol) and methylamine (0.27 g, 8.6 mmol). mp >250 °C.

Example 541: (±)-{7-fluoro-5-[4-(trifluoromethyl)phenyl]-2,3-dihydro-l- benzofuran-2-yl}methyl)methylamine The title compound was prepared (0.14 g, 87%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[{7-fluoro-5-[4- (trifluoromethyl)phenyl]-2,3-dihydro-l -benzofuran-2-yl}methyl 4- methylbenzenesulfonate (0.21g, 0.45 mmol) and methylamine (0.28 g, 9.0 mmol). mp >250 °C.

Example 542: (±)-{7-fluoro~5-[4-methoxyphenyl]-2,3-dihydro-l-benzofuran- 2- yl}methyl)methylamine

The title compound was prepared (0.12 g, 92%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[{7-fluoro-5-[4- methoxyphenyl]-2,3-dihydro-l-benzofuran-2-yl}methyl 4-methylbenzenesulfonate (0.18 g, 0.42 mmol) and methylamine (0.26 g, 8.4 mmol). mp >250 ⁰ C.

Example 543: (+){[7-(2,6-dichlorophenyl)-S-fluoro-2,3-dihydro-l-benzofura n-2- y 1] m ethyl} m ethy lamin e

Treatment of 0.71 g of fraction 1 obtained from the chiral HPLC separation of (±)- [7-(2,6-dichlorophenyl)-5-fluoro-2,3-dihydro-l-benzofuran-2- yl]methyl 4- methylbenzenesulfonate with methylamine (0.47 g, 15.0 mmol) generally according to the procedure described for Example 390 gave 0.42 g (76%) of (+)-{[(7-(2,6- dichlorophenyl)-5-fluoro-2,3-dihydro-l-benzofuran-2-yl]methy l}methylamine as a white solid, hydrochloride salt. [α]o = +7.89 (c 10.0 in methanol); mp 140-142 °C.

Example 544: (-){[7-(2,6-dichlorophenyl)-5-fluoro-2,3-dihydro-l-benzofura n-2- yl]methyl}methylamine

Treatment of 0.79 g of fraction 2 obtained from the chiral HPLC separation of (±)- [7-(2,6-dichlorophenyl)-5-fluoro-2,3-dihydro- 1 -benzofuran-2-yl]methyl 4- methylbenzenesulfonate with methylamine (0.52 g, 16.9 mmol) generally according to the procedure described for Example 390 gave 0.39 g (64%) of (-)-{[(7-(2,6- dichlorophenyl)-5-fluoro-2,3-dihydro-l-benzofuran-2-yl]methy l}methylamine as a white solid, hydrochloride salt, [άffi = -9.02 (c 10.0 in methanol); mp 140-142 ⁰ C.

Example 545: (R)-[7-(2-chloro-phenyl)-5-fluoro-2,3-dihydro-benzofuran-2- y Im ethyl] -methyl-amine

Treatment of (i?)-2-bromomethyl-7~(2-chloro-phenyl)-5-fluoro-2,3- dihydrobenzofuran (0.55 g, 1.6 mmol) generally according to the procedure described for Example 390 gave 0.36 g (77%) of (i?)-[7-(2-chloro-phenyl)-5-fluoro-2,3-dihydro- benzofuran-2-ylmethyl]-methyl-amine as a white foam, hydrochloride salt. [α]β ⁵ = +11.57 (c 7.43 in methanol); Anal, calcd. for C ₁₆ H ₁₅ ClFNOHCl: C, 58.55; H, 4.91; N, 4.27; Found: C, 56.86; H, 5.27; N ₃ 3.91.

Example 546: (R)-[7-(2,6-dichloro-phenyl)-5-fluoro-2,3-dihydro-benzofuran -2- ylmethyl] ethylamine Treatment of (i?)-2-bromomethyl-7-(2,6-dichloro-ρhenyl)-5-fluoro-2,3- dihydrobenzofuran (0.42 g, 1.1 mmol) generally according to the procedure described for Example 390 afforded 0.28 g (74%) of (i?)-[7-(2,6-dichloro-phenyl)-5-fluoro-2,3-

dihydro-benzofuran-2-ylmethyl]ethylamine as a white foam, hydrochloride salt. MS ES [M+H] ⁺ 340.1; [αβ ⁵ = -7.12 (c 7.86 in methanol); Anal, calcd. for C ₁₇ H ₁₆ Cl ₂ FNOHCl: C, 54.21; H, 4.55; N ₅ 3.72. Found: C, 51.85; H, 4.88; N ₅ 3.50.

Example 547: (R)-[7-(2,6-dichloro-phenyl)-5-Fluoro-2,3-dihydro-benzofuran -2- ylm ethyl] dimethylamine

Treatment of (i?)-2-bromomethyl-7-(2,6-dichloro-phenyl)-5-fluoro-2,3- dihydrobenzofuran (0.41 g, 1.1 mmol) and λζiV-dimethylamine (2.0 M in tetrahydrofuran, 5.4 ml) generally according to the procedure described for Example 390 afforded 0.29 g (80%) of (i?)-[7-(2,6-dichloro-phenyl)-5-fluoro-2,3-dihydro-benzofura n-2-ylmethyl]- dimethyl-amine as a white solid, hydrochloride salt. mpl56-158 ⁰ C; [α]β = -21.04 (c 7.71 in methanol); Anal, calcd. for C ₁₇ H ₁₆ Cl ₂ FNOHCl: C, 54.21; H, 4.55; N, 3.72. Found: C, 53.98; H, 4.62; N, 3.56.

Example 548: {[(2R)-7-(5-chloro-2-methylphenyl)-5-fluoro-2,3-dihydro-l- benzofuran-2-yl]methyl} amine

Treatment of (i?)-2-azidomethyl-7-(5-chloro-2-methyl-phenyl)-5-fluoro-2,3 - dihydro-benzofuran (0.40 g, 1.2 mmol) generally according to the procedure described for Example 21 gave {[(2i?)-7-(5-chloro-2-methylphenyl)-5-fluoro-2,3-dihydro-l- benzofuran-2-yl] methyl} amine as a white solid, hydrochloride salt, mp 148-15O ⁰ C; [α]^ ⁵ = +1.45 (c 8.29 in methanol); Anal, calcd. for C ₁₆ H ₁₅ ClFNOHCl: C ₅ 58.55; H, 4.91; N, 4.27. Found: C ₅ 58.55; H ₅ 4.78; N, 3.88.

Example 549: {[(2λ)-7-(4-chloro-2-methylphenyl)-5-fluoro-2,3-dihydro-l- benzofuran-2-yl] methyl} amine

Treatment of (i?)-2-azidomethyl-7-(4-chloro-2-methyl-phenyl)-5-fluoro-2,3 - dihydrobenzo-furan (0.40 g, 1.2 mmol) generally according to the procedure described for Example 21 provided 0.29 g (80%) of {[(2i?)-7-(4-chloro-2-methylphenyl)-5-fluoro-2,3- dihydro-l-benzofuran-2-yl]methyl} amine as a white solid, hydrochloride salt, mp 183- 185 ⁰ C; [aft ⁵ = +7.22 (c 9.14 in methanol); Anal, calcd. for C ₁₆ H _]5 C1FNOHC1: C, 58.55; H, 4.91; N ₅ 4.27. Found: C ₅ 58.55; H ₅ 4.87; N ₅ 4.52.

Example 550: (^-{[V-Cljό-dichloropheny^-S-fluoro-ljS-dihydro-l-benzofura n-I- yl]methyl}amine

Treatment of 0.95 g of fraction 1 obtained from the chiral HPLC separation of (±)- benzyl { [7-(2,6-dichlorophenyl)-5-fluoro-2,3-dihydro-l -benzofuran-2- yl]methyl}carbamate with hydrogen bromide (20 mL, 30 wt.% in acetic acid) generally according to the procedure described for Example 245 gave 0.38 g (57%) of (-)-{[7-(2,6- dichlorophenyl)-5-fluoro-2,3-dihydro-l-benzofuran-2-yl]methy l} amine as a white solid, hydrochloride salt, [α]^ = -21.12 (c 10.0 in methanol); mp 228-230 °C.

Example 551: (+)-{[7-(2,6 dichlorophenyl)-5-fluoro-2,3-dihydro-l-benzofuran-2- yl]methyl}amine

Treatment of 1.3 g of fraction 2 obtained from the chiral HPLC separation of (±)- benzyl {[7-(2,6-dichlorophenyl)-5-fluoro-2,3-dihydro-l-benzofuran-2 - yl]methyl}carbamate trimethylsilyl iodide (2.33 g, 11.6 mmol) generally according to the procedure described for Example 158 gave 0.78 g (77%) of (+)-{[7-(2,6-dichlorophenyl)- 5-fluoro-2,3-dihydro-l-benzofuran-2-yl]methyl} amine as a white solid, hydrochloride salt. [<X] _D = 16.46 (c 10.0 in methanol); mp 217-220 °C.

Example 552: (±)-{2-[6-chloro-7-(2-chlorophenyl)-2,3-dihydro-l-benzofura n-2- yl]ethyl}amine

To a solution of (±)-[6-chloro-7-(2-chlorophenyl)-2,3-dihydro-l-benzofuran-2 - yljmethanol (0.5 g, 1.69 mmol) in toluene (10 mL) was added triphenylphosphine (0.66 g, 2.54 mmol), diethyl azodicarboxylate (0.44 g, 2.54 mmol), and 2-hydroxy-2- methylpropanenitrile (0.21 g, 2.53 mmol) and the reaction mixture was allowed to stir at room temperature for 48 h. The solvent was removed in vacuo to provide a crude oil. Purification by flash column chromatography (silica, ethyl acetate :hexanes 1:9-3:7) provided 0.22 g (43%) of (±)-{2-[6-chloro-7-(2-chlorophenyl)-2,3-dihydro-l-benzofura n- 2-yl]propanenitrile. To a solution of the nitrile in tetrahydrofuran (10 mL) was added borane-tetrahydrofuran (8 mL) and the reaction mixture was heated to reflux for 3 h. The reaction mixture was quenched with 1.0 N aqueous hydrogen chloride (100 mL) and then neutralized with 1.0 N aqueous sodium hydroxide (100 mL). The aqueous layer was extracted with ethyl acetate (2 x 200 mL) and the combined organic extracts were washed

with saturated aqueous sodium chloride (100 niL), dried (magnesium sulfate) and the solvent removed in vacuo. Purification by flash column chromatography (silica, 10% ammonium hydroxide in methanol :dichloromethane 1:9) provided 0.1 g (19%) of (±)-{2- [6-chloro-7-(2-chlorophenyl)-2,3-dihydro-l-benzofuran-2-yl]e thyl}amine as a white solid, hydrochloride salt, mp 211-213 °C.

Example 553: (±)-{2-[7-(2,6-dichlorophenyl)-5-fluoro-2,3-dihydro-l-benzo furan-2- yl]ethyl}amine

Treatment of (±)-[7-(2,6-dichlorophenyl)-5-fluoro-2,3-dihydro- 1 -benzofuran-2- yl]methanol (0.5 g, 1.9 mmol) with triphenylphosphine (1.23 g, 4.67 mmol), diethyl azodicarboxylate (0.82 g, 4.68 mmol), and 2-hydroxy-2-methylpropanenitrile (0.40 g, 4.68 mmol) generally according to the procedure described for Example 552 afforded 0.106 g (15%) of (±)-{2-[7-(2,6-dichlorophenyl)-5-fluoro-2,3-dihydro-l-benzo furan-2- yl] ethyl} amine as a white solid, hydrochloride salt, mp 212-213 °C.

Example 554: (±)-{2-[7-(2-methoxyphenyl)-5-methoxy-2,3-dihydro-l-benzofu ran-2- yl]ethyl}amine

To a solution of (±)-[5-methoxy-7-(2-methoxyphenyl)-2,3-dihydro-l-benzofuran - 2-yl]methyl 4-methylbenzenesulfonate (0.25 g, 0.57 mmol) in dimethylsulfoxide (20 mL) was added sodium cyanide (0.07 g, 1.43 mmol) and the reaction mixture was allowed to stir at 50 ⁰ C for 1 h. The reaction was quenched by the addition of water (10 mL) and extracted with ethyl acetate (2 x 10 mL). The combined organics were washed with water (3 x 20 mL), saturated aqueous sodium chloride (20 mL), dried (magnesium sulfate) and the solvent was removed in vacuo to give a crude oil. Purification by flash column chromatography (silica, ethyl acetate :hexanes 2:8) gave (±)-[5-methoxy-7-(2- methoxyphenyl)-2,3-dihydro-l-benzofuran-2-yl]acetonitrile as a colorless oil. The oil was dissolved in ethanol (30 mL), 28% aqueous ammonium hydroxide (20 mL), and treated with rhodium on alumina (0.1 g, 5 wt. %) generally according to procedure described for Example 1 to afford 0.025 g (13%) of (±)-{2-[5-methoxy-7-(2-methoxyphenyl)-2,3- dihydro-l-benzofuran-2-yl]ethyl}amine as a yellow solid, hydrochloride salt, mp 240-242 °C.

Example 555: (±)-{N-methyl-l-[(7-(2,4,6-trichlorophenyl)-2,3-dihydro-l- benzofuran-2-yI]methanamine

The title compound was prepared (0.424 g, 80%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (±)-[7-(2,4,6-trichlorophenyl)- 2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.68 g, 1.4 mmol) and methylamine (3.1 g, 50.0 mmol). mp 169-172 ⁰ C.

Example 556: (+)-{N-methyI-l-[(7-(2,4,6-trichlorophenyl)-2,3-dihydro-l- benzofuran-2-yl]methanamine

Treatment of 1.48 g of fraction 2 obtained from the chiral HPLC separation of (±)- benzyl { [7-(2,4,6-trichlorophenyl)-2,3 -dihydro- 1 -benzofuran-2- yl]methyl}methylcarbamate with trimethylsilyl iodide (2.48 g, 12.4 mmol) generally according to the procedure described for Example 158 provided 0.125 g (11%) of (+)-{N- methyl-l-[(7-(2,4,6-trichlorophenyl)-2,3-dihydro-l-benzofura n-2-yl]methanamine as a white solid, hydrochloride salt, [α]" = +7.8 (c 10.0 in methanol); mp 93-98 ⁰ C.

Example 557: (-)-{N-methyl-l-[(7-(2,4,6-trichlorophenyl)-2,3-dihydro-l-be nzofuran- 2-yl]methanamine Treatment of 1.41 g of fraction 1 obtained from the chiral HPLC separation of (±)- benzyl { [7-(2,4,6-trichlorophenyl)-2,3-dihydro- 1 -benzofuran-2- yl] methyl }methylcarbamate with trimethylsilyl iodide (2.36 g, 11.8 mmol) generally according to the procedure described for Example 158 gave 0.17 g (15%) of (-)-{N- methyl-1 -[(7-(2,4,6-trichlorophenyl)-2,3 -dihydro- 1 -benzofuran-2-yl]methanamine as a white solid, hydrochloride salt. [<X] _D = -6.2 (c 10.0 in methanol); mp 93-98 ⁰ C.

Example 558: (+)-{[7-(2,6-dimethyIphenyl)-5-fluoro-2,3-dihydro-l-benzofur an-2- yl]methyl}methylamine

The title compound was prepared (0.147 g, 65%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (+)-[7-(2,6-dimethylphenyl)-5- fluoro-2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.50 g, 1.2

mmol) and methylamine (0.372 g, 12.0 mmol). [α]" = +1.6 (c 10.0 in methanol); nip 169-170 °C.

Example 559: (-)-{[7-(2,6-dimethylphenyI)-5-fluoro-2,3-dihydro-l-benzofur an-2- yl]methyl}methylamine

The title compound was prepared (0.298 g, 79%) following the general procedure of Example 390 as a white solid, hydrochloride salt from (-)- [7-(2,6-dimethylphenyl)-5- fluoro-2,3-dihydro-l-benzofuran-2-yl]methyl 4-methylbenzenesulfonate (0.50 g, 1.2 mmol) and methylamine (0.372 g, 12.0 mmol). [α]o ⁵ = -3.0 (c 10.0 in methanol); mp 171- 173 °C.

Example 560: (-)-{[7-(2,6-dimethylphenyl)-5-methoxy-2,3-dihydro-l-benzofu ran-2- yl]methyl}methylamine

Treatment of 0.56 g of fraction 1 obtained from the chiral HPLC separation of (±)- benzyl { [7-(2,6-dimethylphenyl)-5-methoxy-2,3-dihydro- 1 -benzofuran-2- yl]methyl}methylcarbamate with palladium on carbon (0.1 g, 10 wt. %) generally according to the procedure described for Example 1 gave 0.323 g (74%) of (-)-{[7-(2,6- dimethylphenyl)-5-methoxy-2,3-dihydro-l-benzofuran-2-yl]meth yl}methylamine as a white solid, hydrochloride salt. [α]n = -5.9 (c 10.0 in methanol); mp 158-160 °C.

Example 561: (+)-{[7-(2,6-dimethylphenyl)-5-methoxy-2,3-dihydro-l-benzofu ran-2- yl]methyl}methylamine

Treatment of 0.55 g of fraction 2 obtained from the chiral HPLC separation of (±)- benzyl {[7-(2,6-dimethylphenyl)-5-methoxy-2,3-dihydro-l-benzofuran- 2- yl] methyl }methylcarbamate with palladium on carbon (0.1 g, 10 wt.%) generally according to the procedure described for Example 1 gave 0.225 g (53%) of (+) {[7-(2,6- dimethylphenyl)-5-methoxy-2,3-dihydro-l-benzofuran-2-yl]meth yl}methylamine as a white solid, hydrochloride salt. [α]o = +4.51 (c 10.0 in methanol); mp 158-160 °C.

Example 562: (+)-{[5-chIoro-7-(2,5-dichlorophenyl)-2,3-dihydro-l-benzofur an-2- yl]methyl}methylamine

Treatment of 0.9 g of fraction 1 obtained from the chiral HPLC separation of (±)- benzyl {[7-(2,5-dichlorophenyl)-5-chloro-2,3-dihydro-l-benzofuran-2 - yl]methyl}methylcarbamate with hydrogen bromide (20 niL, 30 wt.% in acetic acid) generally according to the procedure described for Example 245 gave 0.598 g (84%) of (+)- { [5-chloro-7-(2,5-dichlorophenyl)-2,3-dihydro- 1 -benzofuran-2- yl]methyl}methylamine as a white solid, hydrochloride salt, [α]β = +14.27 (c 10.0 in methanol); mp 181-183 °C.

Example 563: (-)-{[5-chloro-7-(2,5-dichlorophenyl)-2,3-dihydro-l-benzofur an-2- yl]methyl}methylamine

Treatment of 0.9 g of fraction 2 obtained from the chiral HPLC separation of (±)- benzyl { [7-(2,5-dichlorophenyl)-5-chloro-2,3-dihydro- 1 -benzofuran-2- yl] methyl }methylcarbamate with hydrogen bromide (20 mL, 30 wt.% in acetic acid) generally according to the procedure described for Example 245 gave 0.49 g (68%) of (-)- {[5-chloro-7-(2,5-dichlorophenyl)-2,3-dihydro-l-benzofuran-2 -yl]methyl}methylamine as a white solid, hydrochloride salt, [a]χ> = -7.8 (c 10.0 in methanol); mp 187-189 °C.

Example 564: (-)-{[5-chloro-7-(2,6-dimethylphenyl)-2,3-dihydro-l-benzofur an-2- yl]methyl}methylamine Treatment of 0.65 g of fraction 1 obtained from the chiral HPLC separation of (±)~ benzyl {[5-chloro-7-(2,6-dimethylphenyl)- 2,3-dihydro-l-benzofuran-2- yl]methyl}methylcarbamate with hydrogen bromide (15 mL, 30 wt.% in acetic acid) generally according to the procedure described for Example 245 gave 0.395 g (78%) of (- )-{[5-chloro-7-(2,6-dimethylphenyl)-2,3-dihydro-l-benzofuran -2-yl]methyl}methylamine as a white solid, hydrochloride salt. [α]β ⁵ = -8.4 (c 10.0 in methanol); mp 229-231 ⁰ C.

Example 565: (+)-{[5-chloro-7-(2,6-dimethylphenyl)-2,3-dihydro-l-benzofur an-2- yl]methyl}methylamine

Treatment of 0.65 g of fraction 2 obtained from the chiral HPLC separation of (±)- benzyl {[5-chloro-7-(2,6-dimethylphenyl)- 2,3-dihydro-l-benzofuran-2- yl] methyl }methylcarbamate with hydrogen bromide (15 mL, 30 wt.% in acetic acid) generally according to the procedure described for Example 245 gave 0.37 g (74%) of

(+)-{[5-chloro-7-(2,6-dimethylphenyl)-2,3-dihydro-l-benzofur an-2- yl]methyl}methylamine as a white solid, hydrochloride salt, [α]^ ⁵ = +11.6 (c 10.0 in methanol); mp 229-231 °C.

Example 566: (+)-{[7-(2,3-dimethoxyphenyI)-5-methyl-2,3-dihydro-l-benzofu ran-2- yl]metb.yl}methylamine

Treatment of 0.8 g of fraction 2 obtained from the chiral HPLC separation of (±)- benzyl {[7-(2,3-dimethoxyphenyl)-5-methyl-2,3-dihydro-l-benzofuran- 2- yl]methyl}methylcarbamate with trimethylsilyl iodide (1.05 g, 5.2 mmol) generally according to the procedure described for Example 158 gave 0.16 g (28%) of (+)-{[7-(2,3- dimethoxyphenyl)-5-methyl-2,3-dihydro-l-benzofuran-2-yl]meth yl} amine as a light yellow foam, hydrochloride salt. [α]p ⁵ = +38.89 (c 10.0 in methanol).

Example 567: (-)-{[7-(2,3-dimethoxyphenyl)-5-methyl-2,3-dihydro-l-benzofu ran-2- yl]methyl}methylamine

Treatment of 0.67 g of fraction 1 obtained from the chiral HPLC separation of (±)- benzyl { [7-(2,3-dimethoxyphenyl)-5-methyl-2,3-dihydro-l -benzofuran-2- yl]methyl}methylcarbamate with trimethylsilyl iodide (1.05 g, 5.2 mmol) generally according to the procedure described for Example 158 gave 0.14 g (29%) of (-)-{[7-(2,3- dimethoxyphenyl)-5-methyl-2,3-dihydro-l-benzofuran-2-yl]meth yl}methylamine as a light yellow foam, hydrochloride salt, [α]^ ⁵ = -38.0 (c 10.0 in methanol).

Example 568: (-)-{[7-(2,3-dimethoxyphenyl)-5-fluoro-2,3-dihydro-l-benzofu ran-2- y 1] methyl} methy lamine Treatment of 0.88 g of fraction 1 obtained from the chiral HPLC separation of (±)- benzyl {[7-(2,3-dimethoxyphenyl)-5-fluoro-2,3-dihydro-l-benzofuran- 2- yl]methyl}methylcarbamate with trimethylsilyl iodide (1.55 g, 7.7 mmol) generally according to the procedure described for Example 158 gave 0.37 g (54%) of (-)-{[7-(2,3- dimethoxyphenyl)-5-fluoro-2,3-dihydro-l-benzofuran-2-yl]meth yl}methylamine as a light yellow foam, hydrochloride salt; [a]p = -26.4 (c 10.0 in methanol).

Example 569: (+)-{[7-(2,3-dimethoxyphenyl)-5-fluoro-2,3-dihydro-l-benzofu ran-2- yl] methyl} methy lamine

Treatment of 1.4 g of fraction 2 obtained from the chiral HPLC separation of (±)- benzyl { [7-(2,3-dimethoxyphenyl)-5-fluoro-2,3-dihydro- 1 -benzofuran-2- yl]methyl}methylcarbamate with trimethylsilyl iodide (2.53 g, 12.6 mmol) generally according to the procedure described for Example 158 gave 0.53 g (48%) of (+)-{[7-(2,3- dimethoxyphenyl)-5-fluoro-2,3-dihydro-l-benzofuran-2-yl]meth yl}methylamine as a light yellow foam, hydrochloride salt; [α]^ ⁵ = 25.2 (c 10.0 in methanol).

Example 570: Alternative synthesis of 2R-(-)-7-(2,6-dichlorophenyl)-5-fluoro-2,3- dihydro-2-aminomethylbenzofuran hydrochloride l-Methoxy-4-fluoro-2',6'-dichlorobiphenyl

R = H, Alkyl X = Br, I

To a solution of NaOH (54 g, 1.35 mol) in water (400 mL) heated to 60 °C was added dimethoxyethane (400 mL), then dichlorobromobenzene (Aldrich, 60 g, 0.267 mol) and boronic acid (50 g, 0.294 mol). To the resulting stirred emulsion, solid Pd(PPh ₃ ) ₄ (9.5 g, 8.2 mmol) was added and washed down with 100 mL of DME. The greenish mixture was heated at reflux (ca. 80 °C) while stirred mechanically. The course of reaction was monitored by HPLC. After 2 hr, 9.0 g (0.053 mol) of additional boronic acid and 2.0 g (1.7 mmol) of the catalyst were added to the reaction mixture and the heating was continued for 16 hr longer. More boronic acid (5.8 g, 0.034 mol) and the catalyst (0.5 g, 0.4 mmol) were added at that point and the mixture was kept at reflux for 7 hr longer (23 hr was total reaction time).

The heating was stopped and 600 mL of heptane and 300 mL of water were added. The mixture was allowed to cool to room temperature and then was filtered through Celite. The layers were separated, the organic layer was washed with water, three times with brine, dried with MgSO ₄ and filtered through a pad of Magnesol. The clear colorless solution was concentrated on a rotary evaporator to a colorless oil (weight 72 g). The oil was triturated with 120 mL of heptane which caused crystallization of a white solid. The mixture was left

in a refrigerator overnight, the separated crystals were filtered and dried in air. Yield 51 g, 93% pure. The major impurity was determined to be the homo-coupling product 13. Additional recrystallization of the material from heptane gave crystals of 98% purity. Yield 45 g (62%) as white crystals.

l-Methoxy-2-bromo-4-fluoro-2',6'-dichlorobiphenyl

To a magnetically stirred solution of the arene (38.0 g, 0.140 mol) in 190 mL of dioxane placed into a 500-mL round-bottom flask equipped with a temperature probe, cone, sulfuric acid (38 mL) was added slowly (exothermic mixing, temperature rose to 37 ⁰ C, the solution turned yellow). To the warm solution (the arene would crystallize out of the mixture if it was allowed to cool down), solid NBS (26.7 g, 0.150 mol) was added in one portion (no exothermic heating was observed here). The resulting solution was heated in a mantle at 50 ⁰ C. The reaction progress monitored by HPLC. After 18 hr, only trace amount of the starting arene was detected.

The reaction mixture was allowed to cool to room temperature (r.t), then it was poured onto 400 g of ice (could use lesser amount as it did not melt completely). Heptane (100 mL) was added and the mixture was transferred to the separatory funnel. The aqueous layer was separated and extracted with additional portions of heptane (2 x 100 mL) (toluene could be used instead of heptane as the product started to crystallize; toluene was added to the organic solution to get the product back into the solution). Combined organic solutions were washed once with water (30 mL), then aq. Na ₂ S ₂ O ₃ solution (to remove unreacted NBS, reaction with Kl-starch indicator paper), and, finally, with 1 M aq. NaOH solution (2 x 30 mL) (upon NaOH treatment the mixture turned from yellow to dark-brown but all the color went into the aqueous phase). Light-yellow clear organic solution was dried with MgSO ₄ , filtered through a cotton plug and evaporated in vacuum (bath temp. 60 ⁰ C). The resulting yellow oil was re-dissolved in 55 mL of heptane.

The first batch of crystals (25.5 g) slowly separated from the heptane solution at r.t. and was filtered and dried in air. Purity 98% (HPLC @ 215 nm), white crystals. M.p. 67-69 °C.

The second batch of the product (13.9 g) was isolated from the mother liquor by chilling it in a dry-ice-acetone bath, filtering off the precipitated solid and drying it in a vacuum desiccator over CaSO ₄ . Purity 97% (HPLC area% at 215 nm), white amorphous powder. M.p. 47-56 ⁰ C. Total yield 39.4 g (80%).

¹ H NMR (300 MHz, CDCl ₃ ) 6: 7.42 (m, J = 8.1 Hz, 2H) ¹⁰ , 7.39 (dd, J = 3.0, 7.7 Hz, IH), 7.30 (dd, J = 8.1 Hz, IH), 6.86 (dd, J = 3.0, 8.0 Hz, IH), 3.56 (s, 3H). Protons at 7.42 and 7.30 ppm form a second-order A2B spin system with JAB = 8.1 Hz (determined by NMR simulation). El MS, m/z.

2-[5-Fluoro-3-(2,6-dichlorophenyl)-2-methoxybenzyl]oxiran e

Generation of the Grignard reagent. Aryl bromide (25.0 g, 71.4 mmol) was placed into a 500-mL flask equipped with a magnetic stirrer, nitrogen inlet, temperature probe and a rubber septum. The flask was purged excessively with nitrogen, then left under positive nitrogen pressure. Dry THF (100 mL) was transferred into the flask via a syringe. The solution was chilled in an ice bath to 2 °C.

A solution of i-PrMgCl in THF (1.9 M, Aldrich, 39.5 mL, 75 mmol) was added slowly to the solution in the flask via a syringe (20 min addition time, the temperature was maintained between 2 and 6 °C). The resulting yellowish solution was left in the bath for 18 hr allowing it to reach room temperature. (The reaction is monitored by HPLC analysis of an aliquote quenched by water. Care should be taken not to introduce oxygen into the reaction flask while sampling the solution.)

Reaction with glycidyl tosylate. The solution of the Grignard reagent was chilled to - 30 ⁰ C by placing the flask in a bath with partially frozen dichloroethane (M.p. -45 ⁰ C). CuCN (0.45 g, 5.0 mmol, 7 mol%; Aldrich) was added to the flask via syringe as a slurry in dry

- D\jy -

THF. The resulting mixture was stirred for 1 hr at -30 °C, then (S)-(+)-gl _yc idyl tosylate (15.5 g, 68 rnmol, Aldrich) dissolved in 10 niL of dry THF was added to the solution (addition time 30 min, reaction mixture temperature was maintained between -22 and -29 °C). The reaction was left stirring at -31 °C for 2 hr, then the DCE bath was replaced with a partially frozen o- xylene bath (o-xylene M.p. -25 ⁰ C). Over the next 3 hr the temperature was allowed to reach -18 ⁰ C. HPLC analysis of the quenched aliquot showed complete disappearance of glycidyl tosylate.

To the cold reaction mixture, 100 mL of aq. NH ₄ Cl solution (prepared by 1 : 1 dilution of the saturated solution with water) was added. The phases were separated. The aqueous layer was extracted with 50 mL of MTBE. Combined organic solutions were washed with 30 mL of brine.

Closure of the epoxide. To the solution of the intermediate hydroxytosylate was added aq. solution of NaOH prepared by mixing 20 mL of 10 M stock solution (200 mmol) with 30 mL of water. The resulting bi-phasic mixture was stirred rapidly with a magnetic stirrer so that the mixture was broken into fine emulsion. After 18 hr at room temp, (checked by HPLC) the mixture was transferred to a separatory funnel and the phases were separated. The aqueous phase was extracted with 100 mL of MTBE, combined organic solutions were washed with brine and dried with MgSO ₄ . After filtration through a paper filter, light-yellow solution was evaporated in vacuum to give a mixture the epoxide and des-bromo-arene as a light-yellow oil which solidified upon cooling to room temp. Weight 23.06 g. The mixture was used in the subsequent step without purification.

2)S-3-[5-Fluoro-3-(2,6-dichlorophenyl)-2-methoxyphenyl]-l -N-phthalimidopropan-2-ol

The epoxide (22.6 g of the crude mixture from the previous step, ca. 67 mmol), phthalimide (10.3 g, 70 mmol) and its potassium salt (12.9 g, 70 mmol) were placed in a 250 round-bottom flask equipped with a magnetic stirrer, a nitrogen inlet, and a temperature probe. Dry DMF (100 mL) was added to the mixture. The reaction flask was briefly purged with nitrogen and then was being heated at 75 ⁰ C with stirring for 20 hr (the progress was

monitored by HPLC). Once no starting epoxide was detected, the mixture was allowed to cool to room temp, and then mixed with 200 mL of ice-water slush. The product was extracted with MTBE (2 x 100 mL). The organic solution was washed with solution prepared from 2 parts of 1 M aq. NaOH, 3 parts brine, and 5 parts water (2 x 100 mL), then with brine until neutral pH (Note: The product may start crystallizing during the extractions and washes. In that case it was brought back into solution by adding THF to the mixture). The resulting organic solution was dried with MgSO ₄ , filtered through a paper filter and evaporated in vacuum. The product stalled to crystallize during the evaporation. The volume of the solvent was reduced to ca. 40 mL, then the residue was triturated with 200 mL of hexanes. The white solid was filtered, washed with hexanes and dried in air.

Yield 23.25 g (74% over 3 steps, based on the amount of glycidyl tosylate). M.p. 165-168 °C. η NMR (300 MHz, CDCl ₃ ) 6: 7.86 (m, 2H), 7.72 (m, 2H), 7.43 (m, IH), 7.41 (m, IH), 7.27 (m, IH), 7.08 (dd, J= 3.0, 8.8 Hz, IH), 6.79 (dd, J= 3.0 Hz, 8.1 Hz, IH), 4.23 (d ⁵ , J= 3.3,4.3, 5.7, 7.9, 8.5 Hz, IH), 3.85 (dd, J= 3.3,14.1 Hz, IH), 3.80 (dd, J= 8.5, 14.1 Hz, IH), 3.42 (s, 3H), 2.96 (dd, J = 4.3, 13.9 Hz, IH), 2.92 (dd, J= 7.9, 13.9 Hz, IH), 2.80 (d, J= 5.7 Hz, IH). ES MS, m/z: 474 (M+H) ⁺ , Cl ₂ isotope pattern. Analytical purity: 97% (HPLC area% at 215 ran).

25'-3-[5-Fluoro-3-(2,6-dichlorophenyl)-2-methoxyphenyl]-l -N-phthalimidopropan-2-yl methanesulfonate

In a 500 mL Erlenmeyer flask equipped with a magnetic stirrer, temperature probe and an addition funnel (suspended over the flask without attaching) was placed the product of the preceding step, 25'-3-[5-Fluoro-3-(2,6-dichlorophenyl)-2-methoxyphenyl]-l-iV - ρhthalimidopropan-2-ol, (22.0 g, 46.4 mmol), CH ₂ Cl ₂ (200 mL) and triethylamine (9.7 mL, 70 mmol). Into the addition funnel was placed CH ₂ Cl ₂ (20 mL) and methanesulfonyl chloride (5.4 mL, 70 mL). The solution of MsCl was added dropwise (addition time 10 min) to the stirred solution in the flask (exothermic reaction, temp, rose to 32 ⁰ C by the end of addition).

The reaction mixture was allowed to stir at room temp, for 2 hr (checked by HPLC). White solid separated from the solution over that time.

Water (100 mL) was added to the reaction mixture while stirring it rapidly. About 120 mL of DCM was distilled off on a rotary evaporator. The residue was triturated with 200 mL of hexanes. The solid was filtered and washed excessively with water and hexanes. The cake was dried on the filter for 1 hr then overnight in a vacuum desiccator oven. Yield 25.2 g (98%) as a white fluffy crystals. M.p. >200 ⁰ C (decomp.) ¹ H NMR (300 MHz, CDCl ₃ ) 8: 7.86 (m, 2H), 7.72 (m, 2H), 7.43 (m, 2H), 7.29 (m, IH), 7.09 (dd, J= 3.1, 8.5 Hz, IH), 6.82 (dd, J = 3.1, 8.3 Hz, IH), 5.28 (m, IH) ₅ 4.09 (dd, J = 8.6, 14.6 Hz, IH), 3.90 (dd, J = 3.3, 14.6 Hz, IH), 3.45 (s, 3H), 3.18 (dd, J = 5.4, 14.0 Hz, IH), 3.09 (dd, J - 7.8, 14.0 Hz, IH), 2.65 (s, 3H). ¹³ C NMR (100 MHz, dmso-J ₆ ) 5: 167.6, 157.6 (d, J= 242 Hz), 152.4 (d, J-2 Hz), 134.8, 134.4, 134.3 (d, J= 16 Hz), 131.6, 131.4 (d, J=20 Hz), 131.4, 130.8, 128.3, 123.1, 118.7 (d, J= 22 Hz), 116.7 (d, J= 24 Hz), 78.5, 60.5, 40.8, 37.6, 33.2. ES MS, m/z: 552 (M+H) ⁺ ,C1 ₂ isotope pattern. Analytical purity 99.6% (HPLC area% at 215 nm).

2i?-7-(2,6-DicUorophenyl)-5-fluoro-2,3-dihydro-2-(N-phtha limidomethyl)benzofuran

The product of the preceding step, 2S'-3-[5-Fluoro-3-(2,6-dichlorophenyl)-2- methoxyphenyl]-l-N-phthalimidopropan-2-yl methanesulfonate, (22.1 g, 40.0 mmol) and dichloromethane (200 mL) were placed into a 500-mL flask equipped with a magnetic stirrer, a temperature probe, a nitrogen inlet and a 50-mL addition runnel. The flask and the addition runnel were purged briefly with nitrogen (just in case). The slurry in the flask was chilled in an ice bath to 4 °C. A IM solution OfBBr ₃ in CH ₂ Cl ₂ (Aldrich, 42 mL, 42 mmol) was placed into the addition runnel and was added dropwise to the stirred contents of the flask (addition time 12 min, temp, drifted from 4 to 10 ⁰ C). The stirring was continued allowing the temperature of the reaction mixture to reach 16 ⁰ C over 2-hr period and then at room temp (19 ⁰ C) for 3 hr longer. The reaction progress was monitored by HPLC (1% of unreacted starting material remained, area % at 215 nm). IM

The reaction mixture was quenched by slowly pouring it into the solution prepared from NaHCO ₃ (11 g, 131 mmol) and 200 mL of water (the reaction went fairly slow, no exotherm was observed, no excessive foaming either). Precipitate formed initially in the organic layer but dissolved after ca. 20 min of rapid stirring. After 30 min of stirring, the layers were separated. Aqueous layer was extracted with dichloromethane (2 x 50 mL).

Combined organic solutions were washed with 100 mL of water, then dried with MgSO ₄ The drying agent was filtered off and washed with ethyl acetate. The volume of the filtrate was reduced to about 50 mL on rotary evaporator. The product separated as white or light-yellow solid. The slurry was triturated with 40 mL of a 50:50 hexanes-MTBE mixture, the solid was filtered, washed with the above mixture of solvents and dried on the filter. Yield 14.4 g (82%) as a light-yellow solid. M.p. 222.5-224.5 °C.

¹ H NMR (400 MHz, dmso-J ₆ ) 5: 7.85 (m, 4H), 7.53 (m, 2H), 7.41 (m, IH), 7.19 (dd, J= 2.7, 8.2 Hz, IH), 6.86 (dd, 7 = 2.7, 9.3 Hz, IH), 5.09 (m, IH), 3.79 (m, 2H), 3.43 (dd, J= 9.3, 16.6 Hz, IH), 3.15 (dd, J= 5.9, 16.6 Hz, IH). ¹³ C NMR (100 MHz, dmso-4) 6: 167.8, 156.4 (d, 3 = 237 Hz), 152.2, 134.5,134.4 (d, J = 30 Hz), 133.5,131.5,130.6, 128.6 (d, J - 9.4 Hz), 128.1 (d, J - 3.6 Hz), 123.1, 118.2, 118.1, 114.9 (d, J = 9.3 Hz), 112.9 (d, J = 25 Hz), 80.0, 41.1, 33.2. ES MS, m/z: 442 MH ⁺ , Cl ₂ isotope pattern. Analytical purity: 99.9% (HPLC area % at 215 nm).

2i--7-(2,6-Dichlorophenyl)-5-fluoro-2,3-dihydro-2-aminome thylbenzofurane hydrochloride i) Reagent Solvent .,

ii) HCI/Solvent _:

The product of the preceding step, 2i?-7-(2,6-Dichlorophenyl)-5-fluoro-2,3-dihydro-2- (N-phthalimidomethyl) benzofuran, (12.9 g, 29.2 mmol) was mixed with 70 mL of isopropanol and 15 mL of water. Hydrazine hydrate (55% hydrazine content, Aldrich, 5 mL, 90 mmol) was then added and the reaction mixture was magnetically stirred and heated at gentle reflux for 2 hr. (In case by-product phthalyl hydrazide crystallizes out and gets in a way of stirring it is re-dissolved by adding 3:1 mixture of isopropanol-water. It is very little soluble in isopropanol alone.) Dissolution of the staring material and formation of a clear

solution was an indication that the reaction is done. It was confirmed by HPLC analysis before working up the reaction mixture.

To the hot solution was added 40 mL of 1 M aqueous NaOH and 100 mL of water .

The product was extracted with MTBE (3 x 50 mL). Combined extracts were washed with 60 mL of 0.2 M aq. NaOH ₅ then with water (2 x 50 mL) and finally with brine (50 mL). Resulting clear solution was dried over Na ₂ SO ₄ for 1 hr, filtered through a paper filter and evaporated in vacuum to afford a light-yellow oil (it was slightly opalescent).

The oil was dissolved in 50 mL of EtOAc and to the solution was added rapidly 2 M solution of HCl in diethyl ether (Aldrich, 15 mL, 30 mmol). The salt precipitated rapidly (exothermic) and froze in a single chunk. It was broken up by shaking it with 100 mL of ether, then the slurry was stirred for 30 min in an ice bath. The salt was filtered, washed with

100 mL of ether, dried first on the filter in the stream of air until the filter reached room temp, and then overnight in a vacuum desiccator over CaSO ₄ .

Yield 9.4 g (92%) as white crystals. M.p.231-233 ⁰ C. ¹ H NMR (400 MHz, dmso-d ⁶ ) 6: 8.25 (broad s, 3H), 7.57 (m, J = 8.1 Hz, 2H) , 7.45 (dd, J =

8.1 Hz, IH), 7.24 (dd, J = 2.6, 8.1 Hz, IH), 6.90 (dd, J = 2.6, 9.6 Hz, IH), 5.05 (d ⁴ , J - 9.2, 7.9,

7.0, 4.5 Hz, IH), 3.45 (dd, J = 9.2, 16.6 Hz, IH), 3.17 (dd, J = 7.0, 16.6 Hz), 3.10 (dd, J = 13.4,

4.5 Hz, IH), 3.04 (dd, J = 13.4, 7.9 Hz, IH). Protons at 7.57 and 7.45 ppm form a second- order A ₂ B spin system with J _AB = 8.1 HZ (determined by NMR simulation). ¹³ C NMR (400 MHz, dmso- J ₆ ) 6: 156.4 (d, J = 257Hz), 151.9, 134.5, 134.2, 133.5, 130.5,

128.7 (d, J = 11 Hz), 128.2 (d, J = 21 Hz), 118.3 (d, J = 9 Hz), 115.0 (d, J = 25 Hz), 112.9 (d, J

= 25 Hz), 80.0,42.1,32.8.

ES MS, m/z: 312 (M+H), Cl ₂ isotope pattern.

Enantiomeric purity: 99.4% ee (chiral HPLC on Chiracel OD-H 0.46 x 25 cm, 1 niL/min 90% heptane/DIEA, 10% ethanol, area% at 280 nm).

Analytical purity: 99.8% (HPLC on Prodigy ODS3 0.46 x 15 cm, 1 mL/min water/TFA -

MeCN/TFA 100 min gradient 0-100%, area % at 215 nm). Seventeen impurities in the range of 0.003-0.06 area% were detected totaling 0.19%.

For Ci ₅ H ₁₃ Cl ₃ FNO found C 51.59%, H 3.81%, N 3.87%, anionic Cl 10.49%; calc'd C 51.68%, H 3.76%, N 4.02%, anionic Cl 10.17%.

Example 571: Determination of Binding Affinity and Agonist Activity of Compounds of Formula 1

The ability of the compounds of this invention to act as 5HT _2C agonists and partial agonists was established using several standard pharmacological test procedures; the procedures used and results obtained are provided below. In the test procedures, 5-HT stands for 5-hydroxytryptamine, mCPP stands for meta-chlorophenylpiperazine, and DOI stands for l-(2,5-dimethoxy-4-iodophenyl)isopropylamine.

To evaluate the affinity of various compounds of Formula 1 for activity at the 5- HT _2C receptor, a CHO (Chinese Hamster Ovary) cell line transfected with the cDNA expressing the human 5-hydroxytryptamine-2C (h5-HT ₂ c) receptor was maintained in DMEM (Dulbecco's Modified Eagle Media) supplied with fetal calf serum, glutamine, and the markers: guaninephosphoribosyl transferase (GTP) and hypoxanthinethymidine (HT). The cells were allowed to grow to confluence in large culture dishes with intermediate changes of media and splitting. Upon reaching confluence, the cells were harvested by scraping. The harvested cells were suspended in half volume of fresh physiological phosphate buffered saline (PBS) solution and centrifuged at low speed (900 x g). This operation was repeated once. The collected cells were then homogenized with a polytron at setting #7 for 15 sec in ten volumes of 50 mM Tris.HCl, pH 7.4 and 0.5 mM EDTA. The homogenate was centrifuged at 900 x g for 15 min to remove nuclear particles and other cell debris. The pellet was discarded and the supernatant fluid recentrifuged at 40,000 x g for 30 min. The resulting pellet was resuspended in a small volume of Tris.HCl buffer and the tissue protein content was determined in aliquots of 10-25 μL volumes. Bovine Serum Albumin (BSA) was used as the standard in the protein determination by the method of Lowry et al., (J. Biol. Chem., 193:265 (1951). The volume of the suspended cell membranes was adjusted with 50 mM Tris.HCl buffer containing: 0.1% ascorbic acid, 10 mM pargyline and 4 mM CaCl ₂ to give a tissue protein concentration of 1-2 mg per ml of suspension. The preparation membrane suspension (many times concentrated) was aliquoted in 1 ml volumes and stored at -70 C until used in subsequent binding experiments. Binding measurements were performed in a 96 well microtiter plate format, in a total volume of 200 μL. To each well was added: 60 μL of incubation buffer made in 50

niM Tris.HCl buffer, pH 7.4 and containing 4 niM CaCl ₂ ; 20 μL of [ ¹²⁵ I] DOI (S.A., 2200 Ci/mmol, NEN Life Science).

The dissociation constant, KD of [ ¹²⁵ I] DOI at the human serotonin 5-HT ₂ c receptor was 0.4 nM by saturation binding with increasing concentrations of [ I] DOI. The reaction was initiated by the final addition of 100 μL of tissue suspension containing 50 μg of receptor protein. Nonspecific binding is measured in the presence of 1 μM unlabeled DOI added in 20.0 μL volume. Test compounds were added in 20.0 μL. The mixture was incubated at room temperature for 60 min. The incubation was stopped by rapid filtration. The bound ligand-receptor complex was filtered off on a 96 well unifilter with a Packard ^® Filtermate 196 Harvester. The bound complex caught on the filter disk was dried in a vacuum oven heated to 60° C and the radioactivity measured by liquid scintillation with 40 μL Microscint-20 scintillant in a Packard TopCount ^® equipped with six (6) photomultiplier detectors.

Specific binding is defined as the total radioactivity bound less the amount bound in the presence of 1 μM unlabeled DOI. Binding in the presence of varying concentrations of test drugs is expressed as percent of specific binding in the absence of drug. These results are then plotted as log% bound vs log concentration of test drug. Non linear regression analysis of data points yields both the IC ₅₀ and the Kj values of test compounds with 95% confidence limits. Alternatively, a linear regression line of decline of data points is plotted, from which the IC ₅₀ value can be read off the curve and the Kj value determined by solving the following equation:

IC ₅₀ 1+L/K _D where L is the concentration of the radioactive ligand used and the K _D is the dissociation constant of the ligand for the receptor, both expressed in nM. The following Kj's (95% confidence interval) are provided for various reference compounds:

Compound Ki

Ritanserin 2.0 (1.3 - 3.1) nM

Ketanserin 94.8 (70.7 - 127.0) nM

Mianserin 2.7 (1.9 - 3.8) nM

Clozapine 23.2 (16.0 - 34.0) nM

Methiothepin 4.6 (4.0 - 6.0) nM

Methysergide 6.3 (4.6 - 8.6) nM

Loxapine 33.0 (24.0 - 47.0) nM mCPP 6.5 (4.8 - 9.0) nM

DOI 6.2 (4.9 - 8.0) nM

The ability of the compounds of Formula 1 to produce an agonist response at brain 5-HT ₂ c was assessed by determining their effect on calcium mobilization using the following procedure: CHO cells stably expressing the human 5-HT ₂ c receptor were cultured in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% fetal bovine serum and non-essential amino acids. Cells were plated at a density of 4OK cells/well in 96-well clear-bottom black-wall plates 24 hours prior to the evaluation of 5- HT _2C receptor-stimulated calcium mobilization. For calcium studies, cells were loaded with the calcium indicator dye Fluo-3-AM in Hank's buffered saline (HBS) for 60 minutes at 37 °C. Cells were washed with HBS at room temperature and transferred to the fiuorometric imaging plate reader (FLIPR, Molecular Devices, Sunnyvale, CA) for acquisition of calcium images. Excitation at 488 nni was achieved with an Argon ion laser and a 510-560 nm emission filter was used. Fluorescence images and relative intensities were captured at 1 second intervals and cells were stimulated by addition of agonist after 10 baseline measurements using the internal fluidics module of the FLIPR. An increase in fluorescence counts corresponds to an increase in intracellular calcium. For the evaluation of agonist pharmacology the calcium changes in response to different concentrations of agonist were determined using a maximum minus minimum calculation of the raw fluorescence count data. Calcium changes were then expressed as a percentage of the response observed with a maximally effective concentration of 5-HT. EC ₅₀ values were estimated by non-linear regression analysis of the log-concentration% maximum 5-HT response curves using the 4-parameter logistic function. Preferred compounds are those with an EC ₅₀ of < about 1000 nM, preferably < about 100 nM, more preferably < about 20 nM, still more preferably < about 5 nM, and most preferably < about 2 nM.

The following EC ₅₀ ¹ S are provided for various reference compounds:

Compound EC50

5-HT 0.5 nM

DOI 0.5 nM mCPP 5.4 nM

The results of the standard experimental test procedures described in the preceding paragraphs were as follows:

The compounds of this invention thus have affinity for and agonist or partial agonist activity at brain serotonin 5HT _2c receptors. They are therefore of interest for the treatment of the central nervous system conditions described previously herein.

The entire disclosure of each patent, patent application, and publication cited or described in this document is hereby incorporated by reference.