[TITLE OF THE INVENTION]

PHENYL CARBAMATE COMPOUNDS FOR USE IN PREVENTING OR TREATING A MOVEMENT DISORDER [TECHNICAL FIELD]

The present invention provides a pharmaceutical composition for preventing and/or treating a movement disorder comprising the phenyl carbamate compound as an active ingredient, and a use of the phenyl carbamate compound for preventing and/or treating movement disorder.

[RELATED ART]

Movement Disorders are neurological conditions characterized by either a paucity or lack of movement (such as Parkinson disease) or excessive movement (such as dystonia, dyskinesias, tremor, chorea, ballism, akathisia, athetosis, bradykinesia, postural instability, and tics or Tourette syndrome) (Watts and William eds. (1997) Movement Disorders:

Neurologic Principles and Practice. New "York: McGraw-Hill)

Most of the different types of movement disorders are caused by problems with the nervous system or the brain. One of the most common disorders is known as essential tremor.

Essential tremor is a condition that causes an individual to shake uncontrollably when attempting to use the arms, hands or legs. Most often it occurs during periods where fine motor skills are required, such as holding a delicate object. The disorder can be caused by genetics and often becomes more serious over time.

Like other types of movement disorders, dystonia results from irregularities or damage to the nervous system. People who have dystonia can be identified by exaggerated motion, unintended motion of unrelated parts of the body or uncontrollable and sudden jerking of the arms, legs and head.

Parkinson's disease is one of the most serious types of movement disorders. It is caused by a degenerative disease that affects a dopamine producing region of the brain. An individual with Parkinson's disease can experience uncontrollable tremors, stiffness of the extremities and general physical impairment that prevents easy motor coordination. The cause of the disease is not fully understood although some surgical procedures and drug therapies have helped to reduce symptoms in certain patients. A movement disorder is a neurological disturbance that involves one or more muscles or muscle groups.

Movement disorders include Parkinson's disease, Parkinsonism, other non-related ET or PD tremors (such as head/limb resting, simple kinetic and intention, postural- associated, position-associated, orthostatic, enhanced physiologic, psychogenic, task- associated, voice, cerebellar, rubral and other central and non-classical tremors), restless leg syndrome ( LS), restless arm syndrome(RAS), progressive supranuclear palsy, idiopathic torsion dystonia, focal torsion dystonia, myoclonus, athetosis, abnormal movements in Wilson's disease, Tourette ' s syndrome, paroxysmal movement disorders (including paroxysmal dystonia (eg, kinesgenic paroxystic choreoathetosis, dystonic paroxystic choreoathetosis, intermediate paroxystic choreoathetosis and nocturnal paroxystic choreoathetosis), paroxystic ataxia and paroxystic tremor), drug-induced tremors, postural tremor, tardive dyskinesia and various chronic tremors, tics and dystonias. Different clinically observed movement disorders can be traced to the same or similar areas of the brain. For example, abnormalities of basal ganglia (a large cluster of cells deep in the hemispheres of the brain) are postulated as a causative factor in diverse movement disorders.

Although the present day pharmacopeia offers a variety of agents to treat movement disorders, none of these agents can prevent or cure these conditions. Furthermore, the most effective treatments are often associated with intolerable side effects. There remains a clear- cut need for new treatments for movement disorders that have greater efficacy and fewer side effects than those currently available.

[SUMMARY OF THE INVENTION]

An embodiment provides a pharmaceutical composition for the prevention and the treatment of a movement disorder, comprising a phenyl carbamate compound of the following Chemical Formula 1, an enantiomer or a diastereomer thereof, or a mixture of enantiomers or diastereomers; or a pharmaceutically acceptable salt thereof.

Another embodiment is to provide a method of preventing and/or treating movement disorder in a subject comprising administering a pharmaceutically effective amount of a phenyl carbamate compound represented by Chemical Formula 1 ; a racemate, an enantiomer, a diastereomer, a mixture of enantiomers, or a mixture of diastereomers thereof; or a pharmaceutically acceptable salt thereof, to the subject in need.

Still other embodiment is to provide a phenyl carbamate compound represented by Chemical Formula 1 ; a racemate, an enantiomer, a diastereomer, a mixture of enantiomers, or a mixture of diastereomers thereof; or a pharmaceutically acceptable salt thereof, for use in the prevention and/or treatment of epilepsy or the manufacture of a pharmaceutical composition for preventing and/or treating movement disorder.

[DETAILED DESCRIPTION OF THE EMBODIMENTS]

Continuing its research work in the field of epilepsy, the present inventors, as results of studies on the development of the drugs useful for prevention and/or treatment of movement disorder, found that a substituted phenyl carbamate compounds of the following Chemical Formula 1 exhibits remarkably excellent anti-epilepsy activity in various emulation models and simultaneously has very low toxicity, and completed the invention.

Therefore, an embodiment provides a pharmaceutical composition for prevention and/or treatment of movement disorder, comprising an organic compound, i.e., phenyl carbamate derivatives, more particularly, a phenyl carbamate compound represented by following Chemical Formula 1 ; a racemate, an enantiomer, a diastereomer, a mixture of enantiomers, or a mixture of diastereomers thereof; or a pharmaceutically acceptable salt thereof:

[Chemical Formula 1 ]

wherein,

X is a halogen, for example, chlorine, fluorine, iodine, or bromine,

n, that means the number of substituent X, is an integer from 1 to 5, for example, I or

² '

Rl is a linear or branched alkyl group of C1-C4, for example, methyl, ethyl, isopropyl, or butyl,

A is hydrogen or a carbamoyl derivative represented by ,

H

B is hydrogen, a carbamoyl derivative represented by CJ , trialkyl silyl groups (e.g., a trimethyl silyl (TMS) group, a tri ethyl silyl (TES) group, a triisopropyl silyl (TIPS) group, t-butyl dimethyl silyl (TBDMS) group, and the like), trialkylaryl silyl groups (wherein the total number of alkyl and aryl groups is three; e.g., a t-butyl diphenyl silyl (TBDPS) group and the like), or a trialkyl silyl ether group, wherein each alkyl group may be independently selected from the group consisting of linear, branched, or cyclic C 1-C4 alkyl groups, and each aryl group may be independently selected from the group consisting of C5- C8 aryl groups, preferably a phenyl group,

R2 and R3 may be the same as or different from each other, and independently selected from the group consisting of hydrogen, a linear or branched alkyl group of C1-C4, for example C 1-C3, a cycloalkyl group of C3-C8, for example C3-C7, and benzyl group, and more specifically, R2 and R3 may be the same as or different from each other, and independently selected from the group consisting of hydrogen, methyl group, propyl group, isopropyl group, cyclopropyl group, cyclohexyl group, bicycloheptane group, and benzyl group.

Preferably, in Chemical Formula 1, A is hydrogen and B is carbamoyl group, or A is a carbamoyl group and B is hydrogen.

In the embodiment, in Chemical Formula 1,

if X is F or Br, A and B are not hydrogen at the same time,

if X is chlorine and n is 1 and A and B are hydrogen at the same time, Rl is a C2-C4 linear or branched alkyl group,

if X is chlorine and n is 1 , Rl is methyl, isopropyl or butyl, and

if X is bromine located at 4~postion of the aromatic ring and n is 1 , Rl is methyl, propyl, isopropyl or butyl, and

if A is the carbamoyl group and B is hydrogen, Rl is ethyl, and n is 2 at the same time, two X are located at 2 and 3 positions, 2 and 4 positions, 2 and 5 positions, or 3 and 5 positions of the aromatic ring.

In a concrete embodiment, the phenyl carbamate compound may be selected from the group consisting of:

1 -(2-chlorophenyl)- 1 -hydroxypropyl-2-carbamate,

1 -(2-chlorophenyl)- 1 -hydroxybutyl-2-carbamate,

1 -(2-chlorophenyl)- l-hydroxy-3 -methyl -butyl-2-carbamate,

1 -(2-chlorophenyl)- 1 -hydroxyhexyl-2-carbamate,

1 -(2-chlorophenyl)- 1 -hydroxypropyl-2-N-methylcarbamate,

1 -(2-chlorophenyl)- 1 -hydroxypropyl-2-N-propylcarbamate,

1 -(2-chlorophenyl)- 1 -hydroxypropyl-2-N-isopropylcarbamate,

1 -(2-chlorophenyl)- 1 -hydroxypropyl-2-N-cyclopropylcarbamate, 1 -(2-chlorophenyl)- 1 -hydroxypropyl-2-N-cyclohexyl carbamate,

1 -(2-chlorophenyl)- 1 -hydroxypropyl-2-N-benzylcarbamate,

1 -(2-chlorophenyl)- 1 -hydroxypropyl-2-N-bicyclo[2,2, 1 Jheptanecarbamate,

1 -(2,4-dichlorophenyl)- 1 -hydroxypropyl-2-carbamate,

1 -(2,6-dichlorophenyl)- 1 -hydroxypropyl-2-carbamate,

1 -(2,4-dichlorophenyl)- 1 -hydroxybutyl-2-carbamate,

1 -(2,6-dichlorophenyl)- 1 -hydroxybutyl-2-carbamate

1 -(2,4-dichlorophenyl)- 1 -hydroxy-3-methyl-butyl-2-carbamate,

1 -(2,6-dichlorophenyl)- 1 -hydroxy-3-methyl-butyl-2-carbamate,

I -(2,4-dichlorophenyl)- 1 -hydroxyhexyl-2-carbamate,

1 -(2,6-dichlorophenyl)- 1 -hydroxyhexyl-2-carbamate,

1 -(2-chlorophenyl)-2-hydroxypropyl- 1 -carbamate,

1 -(2-chlorophenyl)-2-hydroxypropyl- 1 -N-methylcarbamate,

1 -(2-chlorophenyl)-2-hydroxypropyl- 1 -N-propylcarbamate,

1 -(2-chlorophenyl)-2-hydroxypropyl- 1 -N-isopropyl carbamate,

1 -(2-chlorophenyl)-2-hydroxypropyl- 1 -N-cyclopropylcarbamate,

1 -(2-chlorophenyl)-2-hydroxypropyl- 1 -N-cyclohexylcarbamate,

l-(2-chlorophenyl)-2-hydroxypropyl-l-N-benzylcarbamate,

1 -(2,4-dichlorophenyl)-2-hydroxypropyl- 1 -carbamate,

l-(2,6-dichlorophenyl)-2-hydroxypropyl-l -carbamate,

1 -(2,4-dichlorophenyl)-2-hydroxybutyl- 1 -carbamate,

1 -(2,6-dichlorophenyl)-2-hydroxybutyl- 1 -carbamate,

l-(2,4-dichlorophenyl)-2-hydroxy-3-methyl-butyl-l -carbamate,

l-(2,6-dichlorophenyl)-2-hydroxy-3-methyl-butyl-l -carbamate,

1 -(2,4-dichlorophenyl)-2-hydroxyhexyl- 1 -carbamate,

1 -(2, 6-dichlorophen yl)-2-hydroxyhexyl- 1 -carbamate,

1 -(2-fluorophenyl)- 1 -hydroxypropyl-2-carbamate,

1 -(2-iodophenyl)- l-hydroxypropyl-2-carbamate,

1 -(2-iodophenyl)- 1 -hydroxybutyl-2-carbamate,

l-(2,3-dichlorophenyl)-l-hydroxypropyl-2-carbamate, and

1 -(2,3-dichlorophenyl)-2-hydroxypropyl- 1 -carbamate.

In another concrete embodiment, the compound may not include 1 -(2-chlorophenyl),2-propanediol, 1 -(2-chlorophenyl)- l-hydroxybutyl-2-carbamate, and l-(2,6 dichlorophenyl)- 1 -hydroxybutyl-2-carbamate.

In this compound, 2 chiral carbons exist at positions 1 and 2 from phenyl group substituted with X; thus, the compound may exist in the form of an enantiomer, a diastereomer, a mixture of enantiomers, or a mixture of diastereomers, as well as a racemate.

In an embodiment, the phenyl carbamate compound is selected from the group consisting of:

1 -(2-chlorophenyl)-(S)- 1 -hydroxypropyl-(S)-2-carbamate,

1 -(2-chlorophenyl)-(R)- 1 -hydroxypropyl-(R)-2-carbamate,

racemate of l-(2-chlorophenyl)-(S)-l -hydroxypropyl-(S)-2-carbamate and l-(2- chlorophenyl)-(R)-l-hydroxypropyl-(R)-2-carbamate,

1 -(2-chlorophenyl)-(R)- 1 -hydroxypropyl-(S)-2-carbamate,

1 -(2-chlorophenyl)-(S)- 1 -hydroxypropyl-(R)-2-carbamate,

1 -(2-chlorophenyl)-(S)- 1 -hydroxybutyl-(S)-2-carbamate,

racemate of l-(2-chlorophenyl)-(S)-l-hydroxybutyl-(S)-2-carbamate and l -(2- chlorophenyl)-(R)- 1 -hydroxybutyl-(R)-2-carbamate,

1 -(2-chlorophenyl)-(S)-l -hydroxy-3 -methyl -butyl-(S)-2-carbamate,

racemate of l -(2-chlorophenyl)-(S)- l -hydroxy-3 -methyl-butyl-(S)-2-carbamate and

1 -(2-chlorophenyl)-(R)- 1 -hydroxy-3 -methyl-butyl-(R)-2-carbamate,

1 -(2-chlorophenyl)-(S)- 1 -hydroxypropyl-(S)-2-N-methylcarbamate,

1 -(2-chlorophenyl)-(S)- 1 -hydroxypropyl-(S)-2-N-propylcarbamate,

1 -(2-chlorophenyl)-(S)- 1 -hydroxypropyl-(R)-2-N-isopropylcarbamate,

1 -(2-chlorophenyl)-(S)- 1 -hydroxypropyl-(R)-2-N-cyclopropylcarbamate,

1 -(2-chlorophenyl)-(S)- 1 -hydroxypropyl-(R)-2-N-cyclohexyl carbamate,

1 -(2-chlorophenyl)-(R)- 1 -hydroxypropyl-(R)-2-N-methylcarbamate,

l-(2-chlorophenyl)-(R)-l -hydroxypropyl-(R)-2-N-propylcarbamate,

1 -(2-chlorophenyl)-(R)- 1 -hydroxypropyl-(R)-2-N-isopropylcarbamate,

1 -(2-chlorophenyl)-(R)- 1 -hydroxypropyl-(R)-2-N-cyclopropyl carbamate,

1 -(2-chlorophenyl)-(R)- 1 -hydroxypropyl-(R)-2-N-cyclohexyl carbamate,

racemate of l-(2-chlorophenyl)-(S)-l-hydroxypropyl-(S)-2-N-methylcarbama te and

1 -(2-chlorophenyl)-(R)- 1 -hydroxypropyl-(R)-2-N-methylcarbamate

racemate of l-(2-chlorophenyl)-(S)- l -hydroxypropyl-(S)-2-N-propylcarbamate and

1 -(2-chlorophenyl)-(R)- 1 -hydroxypropyl-(R)-2-N-propylcarbamate,

racemate of 1 -(2-chlorophenyl)-(S)- 1 -hydroxypropyl-(S)-2-N-isopropylcarbamate and 1 -(2-chlorophenyl)-(R)- 1 -hydroxypropyl-(R)-2-N-isopropylcarbamate,

racemate of 1 -(2-chlorophenyl)-(S)-l -hydroxypropyl-(S)-2-N-cyclopropylcarbamate and l-(2-chlorophenyl)-(R)-l-hydroxypropyl-(R)-2-N-cyclopropylca rbamate,

racemate of l-(2-chlorophenyl)-(S)-l -hydroxypropyl-(S)-2-N-cyclohexyl carbamate and 1 -(2-chlorophenyl)-(R)- 1 -hydroxypropyl-(R)-2-N-cyclohexylcarbamate,

1 -(2-fluorophenyl)-(S)-l -hydroxypropyl-(S)-2-carbamate,

1 -(2-fluorophenyl)-(R)- 1 -hydroxypropyl-(R)-2-carbamate,

1 -(2-iodophenyl)-(S)- 1 -hydroxypropyl-(S)-2-carbamate,

1 -(2-iodophenyl)-(R)- 1 -hydroxypropyl-(R)-2-carbamate, and

l-(2-iodophenyl)-(S)-l-hydroxybutyl-(S)-2-carbamate.

Alternatively, the compound may be in the form of a pharmaceutically acceptable salt. The pharmaceutically acceptable salt may include an additional salt of acid or base, and its stereochemical isomer. For example, the compound may be in the form of an additional salt of an organic or inorganic acid. The salt may not be specially limited, and include any salts that maintain the activities of their parent compounds, with no undesirable effects, in the subject, when they are administered to the subject. Such salts may include inorganic and organic salts, such as salts of acetic acid, nitric acid, aspartic acid, sulfonic acid, sulfuric acid, maleic acid, glutamic acid, formic acid, succinic acid, phosphoric acid, phthalic acid, tannic acid, tartaric acid, hydrobromic acid, propionic acid, benzene sulfonic acid, benzoic acid, stearic acid, lactic acid, bicarbonic acid, bisulfuric acid, bitartaric acid, oxalic acid, butyric acid, calcium edetate, carbonic acid, chlorobezoic acid, citric acid, edetic acid, toluenesulfonic acid, fumaric acid, gluceptic acid, esilic acid, pamoic acid, gluconic acid, methyl nitric acid, malonic acid, hydrochloric acid, hydroiodic, hydroxynaphtholic acid, isethionic acid, lactobionic acid, mandelic acid, mucic acid, naphthylic acid, muconic acid, p- nitromethanesulfonic acid, hexamic acid, pantothenic acid, monohydrogen phosphoric acid, dihydrogen phosphoric acid, salicylic acid, sulfamic acid, sulfanilic acid, methane sulfonic acid, and the like.

The additional salts of base may include salts of akali metal or alkaline earth metal, such as salts of ammonium, lithium, sodium, potassium, magnesium, calcium, and the like; salts having an organic base, such as benzathine, N-methyl-D- glucamine, hydrabamine, and the like; and salts having an amino acid such as arginine, lysine, and the like. In addition, these salts may be converted to a released form by treating with a proper base or acid.

trans olefin Diol

A diol compound used in the synthesis of the carbamate compound may be synthesized by dihydroxylation of a trans-olefin compound. A diol compound having optical activity may be synthesized using a sharpless asymmetric dihydroxylation catalyst.

p

As indicated in the Reaction Formula II, the optically active substance of diol may also be synthesized using an reduction reagent after synthesizing a hydroxy-ketone compound using Haloro-Mandelic acid. In the Reaction Formula II, PG may be Trialkyl Silyl group(TMS, TES, TIPS, TBDMS, TBDPS), Ether group[MOM(Mothoxymethyl ether), MEM(2- Methoxyethoxymethyl ether), BOM(Benzyloxymefhyl ether). MTM(Methylthiomethyl ether), SEM(2-(Trimethylsilyl)ethoxymethyl ether), PMBM(p-Methoxybenzyl ether), THP(Tetrahydropyranyl ether), Allyl ether, Trityl ether, Ester group[Ac(acetate), Bz(Benzoate), Pv(Pivaloate), Cbz(Benzyl carbonate), BOC(t-Butyl carbonate), Fmoc(9- Fulorenylmethyl)carbaonate, Alloc(Allyl Carbonate), Troc(Trichloroehtyl carbonate), or p- Methoxybenzoate, Methyl carbonate, and so on.

trans olefin Diol

A diol compound used in the synthesis of the carbamate compound may be synthesized by dihydroxylation of a trans-olefin compound. A diol compound having optical activity may be synthesized using a sharpless asymmetric dihydroxylation catalyst.

Haloro-Mandelic acid

PG = Protecting Group

As indicated in the Reaction Fonnula II, the optically active substance of diol may also be synthesized using a reduction reagent after synthesizing a hydroxy-ketone compound using Haloro-Mandelic acid. In the Reaction Formula II, PG(protecting group) may be selected from the group consisting of trialkyl silyl group(e.g., a trimethyl silyl (TMS) group, a triethyl silyl (TES) group, a triisopropyl silyl (TIPS) group, t-butyl dimethyl silyl (TBDMS) group, and the like), trialkylaryl silyl groups (wherein the total number of alkyl and aryl groups is three; e.g., a t-butyl diphenyl silyl (TBDPS) group and the like), ester group[Ac(acetate), Bz(benzoate), Pv(pivaloate), Cbz(benzyl carbonate), BOC(t-butyl carbonate), Fmoc(9- fluoroenylmethyl)carbaonate, Alloc(allyl Carbonate), Troc(trichloroethyl carbonate), p- methoxybenzoate, methyl carbonate, and so on] and the like, wherein each alkyl group may be independently selected from the group consisting of linear, branched, or cyclic C1-C4 alkyl groups, and each aryl group may be independently selected from the group consisting of C5-C8 aryl groups, preferably a phenyl group.

Reaction Formula III: Carbamation reaction-1

As a highly selectivity form of regioisomer of single carbamate of diol having halogen substituent at phenyl ring. (Example 1~14 and 36~67 are synthesized by reaction formula III)

Reaction Formula IV: Carbamation reaction-2

Two substances in the form of regioisomers of a single carbamate of diol having halogen substituent at phenyl ring may be separated by flash column chromatography to obtain two kinds of single carbamate compounds. (Example 15-35 and 68-1 15 are synthesized by reaction formula IV)

Reaction Formula V: Protection reaction

In the Reaction Formula V, PG(protecting group) may be selected from the group consisting of trialkyl silyl group(e.g., a trimethyl silyl (TMS) group, a triethyl silyl (TES) group, a triisopropyl silyl (TIPS) group, t-butyl dimethyl silyl (TBDMS) group, and the like), trialkylaryl silyl groups (wherein the total number of alkyl and aryl groups is three; e.g., a t- butyl diphenyl silyl (TBDPS) group and the like), ester group[Ac(acetate), Bz(benzoate), Pv(pivaloate), Cbz(benzyl carbonate), BOC(t-butyl carbonate), Fmoc(9- fiuoroenylmethyl)carbaonate, Alloc(allyl Carbonate), Troc(trichloroethyl carbonate), p- methoxybenzoate, methyl carbonate, and so on] and the like, wherein each alkyl group may be independently selected from the group consisting of linear, branched, or cyclic C1-C4 alkyl groups, and each aryl group may be independently selected from the group consisting of C5-C8 aryl groups, preferably a phenyl group.

In the Reaction Formula IV and V, R4 and R5 may be the same as or different from each other, and independently selected from the group consisting of hydrogen, a linear or branched alkyl group of C1-C4, for example C 1-C3, a cycloalkyl group of C3-C8, for example C3-C7, and benzyl group, and more specifically, R4 and R5 may be the same as or different from each other, and independently selected from the group consisting of hydrogen, methyl group, propyl group, isopropyl group, cyclopropyl group, cyclohexyl group, bicycloheptane group, and benzyl group.

Two substances in the form of regioisomers of a single carbamate of diol having halogen substituent at phenyl ring may be separated by flash column chromatography to obtain two kinds of single carbamate compounds.

Another embodiment provides a method of prevention and/or treatment of a movement disorder, comprising administering a pharmaceutically effective amount of a phenyl carbamate compound represented by Chemical Formula 1 ; a racemate, an enantiomer, a diastereomer, a mixture of enantiomers, or a mixture of diastereomers thereof; or a pharmaceutically acceptable salt thereof, to a subject in need of preventing and/or treating a movement disorder or a movement disorder related symptom. The method can be applied for preventing and/or treating a movement disorder.

The method may further comprise a step of identifying the subject in need of preventing and/or treating a movement disorder prior to the step of administering. Another embodiment provides a phenyl carbamate compound represented by Chemical Formula 1 ; a racemate, an enantiomer, a diastereomer, a mixture of enantiomers, or a mixture of diastereomers thereof; or a pharmaceutically acceptable salt thereof, for use in the prevention and/or treatment of a movement disorder.

Another embodiment provides a use of a phenyl carbamate compound represented by

Chemical Formula 1 ; a racemate, an enantiomer, a diastereomer, a mixture of enantiomers, or a mixture of diastereomers thereof; or a pharmaceutically acceptable salt thereof for the manufacture of a pharmaceutical composition for preventing and/or treating a movement disorder.

In an embodiment, the movement disorder may be selected from ataxia, corticobasal ganglionic degeneration (CBGD), dyskinesia, dystonia, tremors, essential tremor, Parkinsonian tremor, hereditary spastic paraplegia, Huntington's disease, multiple system atrophy, myoclonus, Parkinson's disease, progressive supranuclear palsy, restless legs syndrome, Rett syndrome, spasticity, Sydenham's chorea, other choreas, athetosis, ballism, stereotypy, tardive ' dyskinesia/dystonia, tics, Tourette's syndrome, olivopontocerebellar atrophy (OPCA), diffuse Lewy body disease, hemibalismus, hemi-facial spasm, restless leg syndrome, Wilson's disease, stiff man syndrome, akinetic mutism, psychomotor retardation, painful legs moving toes syndrome, a gait disorder, a drug-induced movement disorder, or other movement disorder. Preferred examples of the movement disorder include tremors, essential tremor, Parkinsonian tremor, Parkinson's disease, dystonia, dyskinesia, tardive dyskinesia/dystonia, olivopontocerebellar atrophy (OPCA), hemi-facial spasm, restless legs syndrome, painful legs moving toes syndrome, a gait disorder, and a drug-induced movement disorder. As used herein, the term "movement disorders" includes akinesias and akinetic-rigid syndromes, dyskinesias and medication-induced parkinsonism (such as neuroleptic-induced parkinsonism, neuroleptic malignant syndrome, neuroleptic-induced acute dystonia, neuroleptic-induced acute akathisia, neuroleptic-induced tardive dyskinesia and medication- induced postural tremor). Examples of "akinetic-rigid syndromes" include Parkinson's disease, drug-induced parkinsonism, postencephalitic parkinsonism, progressive supranuclear palsy, multiple system atrophy, corticobasal degeneration, parkinsonism-ALS dementia complex and basal ganglia calcification. Examples of "dyskinesias" include tremor (including rest tremor, postural tremor and, intention tremor), chorea (such as Sydenham's chorea, Huntington's disease, benign hereditary chorea, neuroacanthocytosis, symptomatic chorea, drug-induced chorea and hemiballism), myoclonus (including generalised myoclonus and focal myoclonus), tics (including simple tics, complex tics and symptomatic tics), and dystonia (including generalised dystonia such as iodiopathic dystonia, drug-induced dystonia, symptomatic dystonia and paroxymal dystonia, and focal dystonia such as blepharospasm, oromandibular dystonia, spasmodic dysphonia, spasmodic torticollis, axial dystonia, dystonic writer's cramp and hemiplegic dystonia). Another "movement disorder" which may be treated according to the present invention is Gilles de la Tourette's syndrome, and the symptoms thereof.

As used herein, the terms "subject" or "patient" are used herein interchangeably and as used herein, refer to a human being, who has been the object of treatment, observation or experiment.

The pharmaceutical composition may be formulated in various forms for oral or parenteral administration. For example, the pharmaceutical composition may be formulated in the oral administration form, such as a tablet, pill, soft or hard capsule, liquid, suspension, emulsion, syrup, granules, elixirs, and the like. In addition to the active ingredient, the oral administration form may further include pharmaceutically acceptable, and conventional components, for example, a diluent such as lactose, dextrose, sucrose, mannitol, sorbitol, cellulose, glycine, and the like; a lubricant such as silica, talc, stearic acid, magnesium or calcium salt thereof, polyethyleneglycol, and the like. In the case that the oral administration form is a tablet, it may further include a binder such as magnesium aluminium silicate, starch paste, gelatin, tragacanth, methylcellulose, sodium carboxymethylcellulose, polyvinylpirrolidine, and the like; and optionally include one or more additives selected from the group consisting of a disintegrant such as starch, agar, arginic acid or sodium salt thereof, an absorbent, a colorant, a flavoring, a sweetener, and the like. Alternatively, the pharmaceutical composition may also be formulated in a parenteral administration form, which can be administered by subcutaneous injection, intravenous injection, intramuscular injection, injection into thoracic cavity, and the like. In order to formulate the parenteral administration form, the pharmaceutical composition may be prepared as a solution or suspension wherein the active ingredient is dissolved in water together with a stabilizer and/or a buffering agent, and such solution or suspension formulation may be prepared as a dosage form in ample or vial.

The pharmaceutical composition may be sterilized, and/or include further additives such as a preservative, a stabilizer, a hydrating agent, an emulsification accelerator, a salt and/or buffering agent for osmoregulation, and the like, and/or further therapeutically effective ingredients. The pharmaceutical composition may be formulated by any conventional method for mixing, granulating, coating, and the like.

The pharmaceutical composition may be administered to a mammal including human, in the pharmaceutically effective amount of 0.01 to 750 mg/kg(body weight), preferably 0.1 to 500 mg/kg(body weight) per one day, based on the active ingredient. The pharmaceutically effective amount may refers to an amount capable of exhibiting a desired effect, i,e., an effect of treating and/or preventing epilepsy. The pharmaceutically effective amount may be administered through oral or parenteral pathway (e.g., an intravenous injection, an intramusclular injection, etc.), one or two or more times per one day.

The pharmaceutically effective amount and the administration pathway of the present pharmaceutical composition may be properly adjusted by a person skilled in the relevant field considering the conditions of the subject (patient), desired effects, and the like. The subject may be a mammal including human or cells and/or tissues obtained therefrom.

[EXAMPLE]

The present invention is further explained in more detail with reference to the following examples. These examples, however, should not be interpreted as limiting the scope of the present invention in any manner.

Preparation Example 1: Synthesis of l-(2-chlorophenyl)-trans-l-propene

48ml of 2-chlorobenzenaldehyde (0.42mol) and 49.7ml of 3-pentanone (0.47mol) were dissolved in 600mL of hexane in flask, and then stirred with raising the temperature. 53.6ml of Boron trifluoride etherate (BF ₃ OEt ₂ , 0.42mol) was added to the resultant under reflux conditions. When the reaction was completed, water was added thereto. After layer separation, the obtained organic layer was washed twice with 1 M sodium hydroxide solution (1M NaOH), and then the separated organic layer was washed with water. The separated organic layer was dehydrated with anhydrous magnesium sulfate (MgS0 ₄ ) and concentrated. The concentrated residue was purified by a silica gel column chromatography to produce the title compound (38g, yield 58%). 1H NMR(400MHz, CDC1 ₃ ) 51.94(d, J=4.8Hz, 3H), 6.24(m, lH), 6.78(d, J=14Hz, 1H), 7.11-7.5 l (m, 4H)

Preparation Example 2: Synthesis of l-(2-chlorophenyl)-trans-l-butene

The substantially same method as described in Preparation Example 1 was conducted, except that 3-heptanone was used instead of 3-pentanone, to obtain the title compound (2.9g. yield 83%).

Ή NMR(400MHz, CDC1 ₃ ) 61.14(d, J=7.6Hz, 3H), 2.29~2.33(m, 2H), 6.28(dt, J=16Hz, 6.4Hz, 1 H), 6.78(d, J=15.6Hz, 1H), 7.13~7.54(m, 4H)

Preparation Example 3: Synthesis of l-(2-chlorophenyl)-3-methyl-trans-l- butene

The substantially same method as described in Preparation Example 1 was conducted, except that 2,6-dimethyl-heptan-4-one was used instead of 3-pentanone, to obtain the title compound (8.0g, yield 50-90%).

Ή NMR(400MHz, CDC1 ₃ ) 61.14(d, J=6.8Hz, 6H), 2.25~2.57(m, 1 H), 6.20(dd, J=16Hz, 7.2Hz, 1H), 7.64(d, J=16Hz, 1H), 7.12~7.54(m, 4H)

Preparation Example 4: Synthesis of l-(2-chlorophenyl)-trans-l-hexene

The substantially same method as described in Preparation Example 1 was conducted, except that 6-undecanone was used instead of 3-pentanone, to obtain the title compound ( Og, yield 85%).

Ή NMR(400MHz, CDC1 ₃ ) 50.96(t, J=7.2Hz, 3Ή), 1.33~1.56(m, 4H), 2.26~2.32(m,

4H), 6.24(dt, J=15.6Hz, 7Hz, 1H), 6.78(d, J=16Hz, 1H), 7.13~7.54(m, 4H) ple 5: Synthesis of l-(2,4-dichlorophenyl)-trans-l-propene

The substantially same method as described in Preparation Example 1 was conducted, except that 2,4-dichlorobenzenaldehyde was used instead of 2-chlorobenzenaldehyde, to obtain the title compound (2.4g, yield 57%).

Ή NMR(400MHz, CDCI3) 81.95(dd, J=6.8Hz, 1.6Hz, 3H), 6.24(m, 1H), 6.72(d, J=15.6Hz, 1H), 7.18~7.44(m, 3H) le 6: Synthesis of l-(2,4-dichlorophenyl)-trans-l-butene

The substantially same method as described in Preparation Example 5 was conducted, except that 3-heptanone was used instead of 3-pentanone, to obtain the title compound (2.1g, yield 90%).

Ή NMR(400MHz, CDC1 ₃ ) 51.14(d, J=7.6Hz, 3H), 2.20~2.33(m, 2H), 6.26(dt, J=16Hz, 6.8Hz, 1 H), 6.70(d, J=15.6Hz, 1 H), 7.18~7.46(m, 3H)

Preparation Example 7: Synthesis of l-(2,6-dichlorophenyl)-3-methyl-trans-l- butene

The substantially same method as described in Preparation Example 5 was conducted, except that 2,6-dimethyl-heptan-4-one was used instead of 3-pentanone, to obtain the title compound (0.23g, yield 10-40%).

Ή NMR(400MHz, CDC1 ₃ ) 61.15(d, J=6.8Hz, 6H), 2.53~2.58(m, 1H), 6.19(dd,

J=16.4Hz, 6.8Hz, 1 H), 6.31(d, J=16.4Hz, 1H), 7.18~7.46(m, 3H)

Preparation Example 8: Synthesis of l-(2,4-dichlorophenyl)-trans-l-hexene

The substantially same method as described in Preparation Example 5 was conducted, except that 6-undecanone was used instead of 3-pentanone, to obtain the title compound (3.2g, yield 40-80%).

Ή NMR(400MHz, CDC1 ₃ ) 50.96(t, J=7.2Hz, 3H), 1.38-1.52(m, 4H), 2.25-2.31(m, 2H), 6.22(dt, J=l5.6Hz, 6.8Hz, 1H), 6.70(d, J=15.6Hz, 1H), 7.18-7.46(m, 3H)

Preparation Example 9: Synthesis of l-(2,6-dichlorophenyl)-trans-l-propene

The substantially same method as described in Preparation Example 1 was conducted, except that 2,6-dichlorobenzenaldehyde was used instead of 2-chlorobenzenaldehyde, to obtain the title compound (0.4g, yield 10-40%).

Ή NMR(400MHz, CDC1 ₃ ) 51.98(d, J=8Hz, 3H), 6.23-6.3 l(m, 1H), 6.40(d, J=16Hz, 1H), 7.05~7.32(m, 3H) ample 10: Synthesis of l-(2,6-dichlorophenyl)-trans-l-butene The substantially same method as described in Preparation Example 9 was conducted, except that 3-heptanone was used instead of 3-pentanone, to obtain the title compound (1.2g, yield 10-40%).

Ή NMR(400MHz, CDC1 ₃ ) 51.17(t, J=7.6Hz, 3H), 2.30~2.37(m, 2H), 6.29(dt, J=16.4Hz, 6Hz, I H), 6.37(d, J=16.4Hz, 1 H), 7.05~7.32(m, 3H)

Preparation Example 11: Synthesis of l-(2,6-dichlorophenyl)-3-methyl-trans-l- butene

The substantially same method as described in Preparation Example 9 was conducted, except that 2,6-dimethyl-heptan-4-one was used instead of 3-pentanone, to obtain the title compound (0.23g, yield 10-40%).

Ή NMR(400MHz, CDC1 ₃ ) 51.15(d, J=6.8Hz, 6H), 2.53~2.58(m, 1H), 6.19(dd, J=16.4Hz, 6.8Hz, 1H), 6.31 (d, J=16.4Hz, 1H), 7.05~7.32(m, 3H)

Preparation Example 12: Synthesis of l-(2,6-dichlorophenyl)-trans-l-hexene

The substantially same method as described in Preparation Example 9 was conducted, except that 6-undecanone was used instead of 3-pentanone, to obtain the title compound (0.2g, yield 10-40%).

Ή NMR(400MHz, CDC1 ₃ ) 60.99(t, J=7.2Hz, 3H),1.14~1.59(m, 4H), 2.30~2.36(m, 2H), 6.24(dt, J=16Hz, 6.6Hz, 1H), 6.38(d, J=16.4Hz, 1H), 7.05~7.33(m, 3H)

Preparation Example 13: Synthesis of l-(2,3-dichlorophenyl)-trans-l-propene

The substantially same method as described in Preparation Example 1 was conducted, except that 2,3 -dichlorobenzenaldehyde was used instead of 2-chlorobenzenaldehyde, to obtain the title compound (0.2g, yield 10-40%).

Ή NMR(400MHz, CDC1 ₃ ) 61.94(d, J=4.8Hz, 3H), 6.24(m, 1H), 6.78(d, J=14Hz, 1H), 7.1 1~7.51(m, 3H)

Preparation Example 14: Synthesis of l-(2-chlorophenyl)-(S,S)-l,2-propanediol

l -(2-chlorophenyl)-trans-l -propene(1.5g, Preparation Example 1) was dissolved in 30mL of the mixture of t-BuOH/H ₂ 0 (1 : 1 (V/V)). At 0 ^° C , AD-mix-a (Aldrich, U.S.A.) (13.7g) and methane sulfone amide (CH ₃ S0 ₂ NH ₂ , 0.76g, 0.0080mol) were added thereto and stirred for overnight. When the reaction was completed, the obtained product was washed with an aqueous solution of sodium sulfite (Na ₂ S0 ₃ ) and ethylacetate (EA). Then, the organic layer was dehydrated with anhydrous magnesium sulfate (MgS0 ₄ ), filtrated, and concented under reduced pressure. The concentrated residue was purified by a silica gel column chromatography to produce the title compound (1.65g, yield 90%).

Ή NMR(400MHz, CDCI3) 51.20(d, J=6.4Hz, 3H), 2.48(d, J=4.0Hz 1H), 2.92(d,

J=4.4Hz, 1H), 3.93~3.97(m, lH), 4.97(t, J=4.8Hz, 1 H), 7.22~7.51(m, 4H)

l ³ CNMR( 100MHz,CDCl ₃ ) 518.8, 71.5, 74.4, 127.1, 128.1, 128.9, 129.5, 132.6, 138.9

Preparation Example 15: Synthesis of l-(2-chlorophenyl)-(R,R)-l,2-propanediol

l -(2-chlorophenyl)-trans- l-propene (2.5g, Preparation Example 1) was dissolved in 50mL of the mixture of t-BuOH/H ₂ 0 (1 : 1 (V/V)). At 0 ^° C , AD-mix-a (Aldrich, U.S.A.) (23.5g) and methane sulfone amide (CH ₃ S0 ₂ NH ₂ , 1.27g, 0.013mol) were added thereto and stirred for overnight. When the reaction was completed, the obtained product was washed with an aqueous solution of sodium sulfite (Na ₂ S0 ₃ ) and ethylacetate (EA). Then, the organic layer was dehydrated with anhydrous magnesium sulfate (MgS0 ₄ ), filtrated, and concented under reduced pressure. The concentrated residue was purified by a silica gel column chromatography to produce the title compound (2.96g, yield 90%).

Ή NMR(400MHz, CDCI3) 61.20(d, J=6.4Hz, 3H), 2.48(d, J=4.0Hz, 1H), 2.92(d, J=4.4Hz, 1 H), 3.93~3.97(m, 1 H), 4.97(t, J=4.8Hz, 1 H), 7.22~7.51 (m, 4H)

Preparation Example 16: Synthesis of the mixture of l-(2-chlorophenyl)-(S,S)- 1,2-propanediol and l-(2-chlorophenyl)-(R,R)-l,2-propanediol

l-(2-chlorophenyl)-trans-l -propene(6.53g, Preparation Example 1) was dissolved in 45mL of the mixture of acetone/t-BuOH/H ₂ 0(5: l : l V/V). At the room temperature, N- methylmo holi e-N-oxide (7.5 lg) and OsO ₄ (0.54g) were added thereto and stirred for 2-3 hours. When the reaction was completed, the obtained product was washed with water and methylenechloride (MC). Then, the organic layer was dehydrated with anhydrous magnesium sulfate (MgS0 ₄ ), filtrated, and concented under reduced pressure. The concentrated residue was purified by a silica gel column chromatography to produce the title compound (6.42g, yield 80%).

Ή NMR(400MHz, CDC1 ₃ ) 51.20(d, J=6.4Hz, 3H), 2.48(d, J=4.0Hz, 1H), 2.92(d, J=4.4Hz, 1H), 3.93~3.97(m, 1H), 4.97(t, J=4.8Hz, 1H), 7.22~7.51(m, 4H)

Preparation Example 17: Synthesis of l-(2-chlorophenyl)-(S,S)-l,2-butanediol

The substantially same method as described in Preparation Example 14 was conducted, except that l -(2-chlorophenyl)-trans-l-butene(Preparation Example 2) was used instead of l-(2-chlorophenyl)-trans-l-propene(Preparation Example 1), to obtain the title compound (0.36g, yield 95%).

Ή NMR(400MHz, CDC1 ₃ ) 61.01 (t, J=7.4Hz, 3H), 1.52~1.65(m, 2H), 2.01 (d, J=4.4Hz, 1 H), 2.74(d, J=5.2Hz, 1 H), 3.69~3.75(m, 1H), 5.05(t, J=5.0Hz, 1H), 7.23~7.54(m, 4H)

Preparation Example 18: Synthesis of l-(2-chlorophenyl)-(R,R)-l,2-butanediol

The substantially same method as described in Preparation Example 15 was conducted, except that l-(2-chlorophenyl)-trans-l -butene(Preparation Example 2) was used instead of l-(2-chlorophenyl)-trans- l-propene(Preparation Example 1 ), to obtain the title compound (0.84g, .yield 60-95%).

Ή NMR(400MHz, CDC1 ₃ ) 61.01(t, J=7.4Hz, 3H), 1.52-~1.65(m, 2H), 2.01 (d, J=4.4Hz, 1H), 2.74(d, J=5.2Hz, lH), 3.69~3.75(m, 1H), 5.05(t, J=5.0Hz, 1H), 7.23~7.54(m, 4H)

Preparation Example 19: Synthesis of the mixture of l-(2-chIorophenyl)-(S,S)- 1,2-butanediol and l-(2-chlorophenyl)-(R,R)-l,2-butanediol

The substantially same method as described in Preparation Example 16 was conducted, except that l-(2-chlorophenyl)-trans-l -butene(Preparation Example 2) was used instead of l -(2-chlorophenyl)-trans- l-propene(Preparation Example 1 ), to obtain the title compound (5.1 g, yield 60-90%).

Ή NMR(400MHz, CDC1 ₃ ) 51.01(t, J=7.4Hz, 3H), 1.52~1.65(m, 2H), 2.01 (d, J=4.4Hz, 1 H), 2.74(d, J=5.2Hz, 1H), 3.69~3.75(m, 1H), 5.05(t, J=5.0Hz, 1H), 7.23~7.54(m, 4H)

Preparation Example 20: Synthesis of l-(2-chlorophenyl)-3-methyl-(S,S)-l,2- butanediol

The substantially same method as described in Preparation Example 14 was conducted, except that l-(2-chlorophenyl)-3 -methyl-trans- 1 -butene(Preparation Example 3) was used instead of l-(2-chlorophenyl)-trans- l -propene(Preparation Example 1), to obtain the title compound (0.96g, yield 60-90%). Ή NMR(400MHz, CDC1 ₃ ) 51.07(t, J=7.2Hz, 6H), 1.83-1.89(m, 1H), 1.92(d, J=5.6Hz, 1H), 2.69(d, J=6.4Hz, 1H), 3.53~3.56(m, 1H), 5.22~5.25(m, 1H), 7.23~7.55(m, 4H)

Preparation Example 21: Synthesis of l-(2-chlorophenyl)-3-methyl-(R,R)-l,2- butanediol

The substantially same method as described in Preparation Example 15 was conducted, except that l -(2-chlorophenyl)-3 -methyl-trans- l-butene(Preparation Example 3) was used instead of l-(2-chlorophenyl)-trans-l-propene(Preparation Example 1), to obtain the title compound (4.2g, yield 60-90%).

Ή NMPv(400MHz, CDCI3) 61.07(t, J=7.2Hz, 6H), 1.82~1.90(m, 1H), 1.93(d, J=5.6Hz, 1H), 2.79(d, J=6Hz, 1H), 3.53~3.57(m, 1H), 5.23~5.25(m, 1 H), 7.23~7.54(m, 4H)

Preparation Example 22: Synthesis of the mixture of l-(2-chlorophenyi)-3- methyl- -l,2-butanediol and l-(2-chlorophenyl)-3-methyl-(R,R)-l,2-butanediol

The substantially same method as described in Preparation Example 16 was conducted, except that l-(2-chlorophenyl)-3 -methyl-trans- 1 -butene(Preparation Example 3) was used instead of l-(2-chlorophenyl)-trans-l -propene(Preparation Example 1), to obtain the title compound (0.8g, yield 60-90%).

1H NMPv(400MHz, CDC1 ₃ ) 51.07(t, J=7.2Hz, 6H), 1.83~1.90(m, 1 H), 1.92(d, J=5.6Hz, 1H), 2.69(d, J=6.4Hz, 1H), 3.53~3.56(m, lH), 5.22~5.25(m, 1H), 7.23~7.55(m, 4H)

Preparation Example 23: Synthesis of l-(2-chlorophenyl)-(S,S)-l,2-hexanediol The substantially same method as described in Preparation Example 14 was conducted, except that l -(2-chlorophenyl)-trans-l-hexene(Preparation Example 4) was used instead of l-(2-chlorophenyl)-trans-l-propene(Preparation Example 1), to obtain the title compound (0.37g, yield 90%).

Ή NMR(400MHz, CDC1 ₃ ) 50.90(t, J=7.2Hz, 3H), 1.35~1.65(m, 6H), 2.08(d, J=4.4Hz, I H), 2.71(d, J=5.2Hz, IH), 3.78~3.83(m, IH), 5.04(t, J=5.0Hz, IH), 7.23~7.53(m, 4H)

Preparation Example 24: Synthesis of l-(2-chlorophenyl)-(R,R)-l,2-hexanediol

The substantially same method as described in Preparation Example 15 was conducted, except that l -(2-chlorophenyl)-trans-l -hexene(Preparation Example 4) was used instead of l-(2-chlorophenyl)-trans-l-propene(Preparation Example 1), to obtain the title compound (4.2g, yield 60-90%).

Ή NMR(400MHz, CDC1 ₃ ) , 50.91 (t, J=6.6Hz, 3H), 1.35~1.65(m, 6H), 2.08(d,

J=4.8Hz, IH), 2.70(d, J=5.2Hz, IH), 3.80~3.83(m, IH), 5.05(t, J=5.0Hz, IH), 7.24~7.56(m, 4H)

Preparation Example 25:- Synthesis of the mixture of l-(2-chlorophenyl)-(S,S)- 1,2-hexanedioI and l-(2-chlorophenyl)-(R,R)-l _? 2-hexanediol

The substantially same method as described in Preparation Example 16 was conducted, except that l-(2-chlorophenyl)-trans- l -hexene(Preparation Example 4) was used instead of l-(2-chlorophenyl)-trans- l -propene(Preparation Example 1 ), to obtain the title compound (7.9g, yield 60-90%).

Ή NMR(400MHz, CDC1 ₃ ) 50.90(t, J=7.2Hz, 3H), 1.26~1.55(m, 6H), 2.08(d, J=4.4Hz, I H), 2.71 (d, J-5.6Hz, I H), 3.78-3.84(m, I H), 5.04(t, J=3.2Hz, IH), 7.24-7.55(m, 4H) Preparation Example 26: Synthesis of l-(2,4-dichlorophenyl)-(S,S)-l,2- propanediol

The substantially same method as described in Preparation Example 14 was conducted, except that l-(2,4-ichlorophenyl)-trans- l-propene(Preparation Example 5) was used instead of l-(2-chlorophenyl)-trans-l-propene(Preparation Example 1), to obtain the title compound (0.33g, yield 60-95%).

Ή NMR(400MHz, CDC1 ₃ ) 61.22(d, J=6.4Hz, 3H), 2.10(d, J=4.4Hz, 1H), 2.71(d, J=4.8Hz, l H), 3.90~3.95(m, 1H), 4.94(t, J=5.0Hz, 1H), 7.31(dd, J=2.0Hz, J=8.0Hz, 1H), 7.40(d, J=2.0Hz, 1H), 7.49(d, J=8.4Hz, 1H)

Preparation Example 27: Synthesis of l-(2,4-dichlorophenyl)-(R,R)-l,2- propanediol

The substantially same method as described in Preparation Example 15 was conducted, except that l -(2,4-ichlorophenyl)-trans-l -propene(Preparation Example 5) was used instead of l-(2-chlorophenyl)-trans- l-propene(Preparation Example 1), to obtain the title compound (0.45g, yield 60-95%).

Ή NMR(400MHz, CDC1 ₃ ) 51.22(d, J=6.4Hz, 3H), 2.10(d, J=4.4Hz, I H), 2.71 (d, J=4.8Hz, 1 H), 3.90~3.95(m, 1H), 4.94(t, J=5.0Hz, 1H), 7.31~7.49(m, 3H)

Preparation Example 28: Synthesis of the mixture of l-(2,4-dichlorophenyl)- (S,S)-l,2-propanediol and l-(2,4-dichlorophenyl)-(R,R)-l,2-propanediol

The substantially same method as described in Preparation Example 16 was conducted, except that l-(2,4-ichlorophenyl)-trans-l-propene(Preparation Example 5) was used instead of l-(2-chlorophenyl)-trans-l-propene(Preparation Example 1), to obtain the title compound (0.45g, yield 60-95%).

1H NMR(400MHz, CDC1 ₃ ) 61.22(d, J=6.4Hz, 3H), 2.10(d, J=4.4Hz, 1H), 2.71(d, J=4,8Hz, 1H), 3.90~3.95(m, 1H), 4.94(t, J=5.0Hz, 1H), 7.31~7.49(m, 3H)

Preparation Example 29: Synthesis of l-(2,4-dichlorophenyl)-(S,S)-l,2- butanediol

The substantially same method as described in Preparation Example 14 was conducted, except that l-(2,4-dichlorophenyl)-trans-l-butene(Preparation Example 6) was used instead of l-(2-chlorophenyl)-trans-l-propene(Preparation Example 1), to obtain the title compound (0.32g, yield 90%).

Ή NMR(400MHz, CDC1 ₃ ) 51.02(t, J=7.4Hz, 3H), 1.54~1.61(m, 2H), 2.07(d, J=4.8Hz, 1H), 2.74(d, J=4.8Hz, l H), 3.65~3.68(m, 1H), 5.01 (t, J=5.0Hz, 1H), 7.31~7,49(m, 3H)

Preparation Example 30: Synthesis of l-(2,4-dichlorophenyl)-(R,R)-l,2- butanediol

The substantially same method as described in Preparation Example 15 was conducted, except that l-(2,4-dichlorophenyl)-trans-l-butene(Preparation Example 6) was used instead of l-(2-chlorophenyl)-trans-l-propene(Preparation Example 1), to obtain the title compound (0.43g, yield 60-90%).

Ή NMR(400MHz, CDC1 ₃ ) 51.02(t, J=7.4Hz, 3H), 1.54~1.61(m, 2H), 2.07(d, J=4.8Hz, 1H), 2.74(d, J=4.8Hz, l H), 3.65~3.68(m, 1H), 5.01 (t, J=5.0Hz, 1H), 7.31~7.49(m, 3H)

Preparation Example 31: Synthesis of the mixture of l-(2,4-dichlorophenyl)- (S,S)-l,2-butanediol and l-(2,4-dichlorophenyl)-(R,R)-l,2-butanediol

The substantially same method as described in Preparation Example 16 was conducted, except that l-(2,4-dichlorophenyl)-trans-l-butene(Preparation Example 6) was used instead of l-(2-chlorophenyl)-trans- l-propene(Preparation Example 1), to obtain the title compound (0.33g, yield 60-90%).

Ή NMR(400MHz, CDC1 ₃ ) 51.02(t, J=7.4Hz, 3H), 1.54-1.61 (m, 2H), 2.07(d, J=4.8Hz, 1H), 2.74(d, J=4.8Hz, lH), 3.65-3.68(m, 1H), 5.01 (t, J=5.0Hz, 1 H), 77.31~7.49(m, 3H)

Preparation Example 32: Synthesis of l-(2,4-dichlorophenyl)-3-methyl-(S,S)-l,2- butanediol

The substantially same method as described in Preparation Example 14 was conducted, except that l -(2,4-dichlorophenyl)-3-methyl-trans-l -butene(Preparation Example 7) was used instead of l-(2-chlorophenyl)-trans-l-propene(Preparation Example 1), to obtain the title compound (0.25g, yield 60-95%).

Ή NMR(400MHz, CDC1 ₃ ) ^' 61.00(d, J=6.8Hz, 6H), 1.60~1.65(m, 1 H), 2.35(d, J=4.0Hz, 1H), 3.12(d, J=8.4Hz, 1H), 4.13-4.18(m, 1H), 5.36(t, J=7.6Hz, 1H), 7.17-7.35(m, 3H)

Preparation Example 33: Synthesis of l-(2,4-dichlorophenyl)-3-methyl-(R,R)- 1,2-butanediol

The substantially same method as described in Preparation Example 15 was conducted, except that l-(2,4-dichlorophenyl)-3-methyl-trans-l-butene(Preparation Example 7) was used instead of l-(2-chlorophenyl)-trans- l-propene(Preparation Example 1 ), to obtain the title compound (0.36g, yield 60-95%). Ή NMR(400MHz, CDC1 ₃ ) 61.00(d, J=6.8Hz, 6H), 1.60~1.65(m, l H), 2.35(d, J=4.0Hz, 1H), 3.12(d, J=8.4Hz, 1H), 4.13~4.18(m, 1H), 5.36(t, J=7.6Hz, 1H), 7.17~7.35(m, 3H)

Preparation Example 34: Synthesis of the mixture of l-(2,4-dichlorophenyl)-3- methyl- -l,2-butanediol and l-(2,4-dichlorophenyl)-3-methyl-(R,R)-l,2-butanediol

The substantially same method as described in Preparation Example 16 was conducted, except that l-(2,4-dichlorophenyl)-3-methyl-trans-l-butene(Preparation Example 7) was used instead of l-(2-chlorophenyl)-trans-l-propene(Preparation Example 1), to obtain the title compound (0.26g, yield 60-95%).

Ή NMPv(400MHz, CDC1 ₃ ) 61.00(d, J=6.8Hz, 6H), 1.60~1.65(m, l H), 2.35(d, J=4.0Hz, 1H), 3.12(d, J=8.4Hz, 1H), 4.13~4.18(m, 1H), 5.36(t, J=7.6Hz, 1H), 7.17~7.35(m, 3H)

Preparation Example 35: Synthesis of l-(2,4-dichlorophenyI)-(S,S)-l,2- hexanediol

The substantially same method as described in Preparation Example 14 was conducted, except that l-(2,4-dichlorophenyl)-trans-l-hexene(Preparation Example 8) was used instead of l-(2-chlorophenyl)-trans-l-propene(Preparation Example 1), to obtain the title compound (l . l g, yield 60-90%).

Ή NMR(400MHz, CDCI ₃ ) 50.89~0.93(m, 3H), 1.30~1.39(m, 2H), 1.49~1.52(m, 2H), 1.56~1.62(m, 2H), 2.05(d, J=5.2Hz, 1 H), 2.74(d, J=5.2Hz, 1 H), 3.72~3.77(m, 1 H), 4.98(t, J=4.8Hz, 1H), 7.28-7.50(m, 3H)

Preparation Example 36: Synthesis of l-(2,4-dichlorophenyl)-(R,R)-l,2- hexanediol

The substantially same method as described in Preparation Example 15 was conducted, except that l-(2,4-dichlorophenyl)-trans-l-hexene(Preparation Example 8) was used instead of l-(2-chlorophenyl)-trans-l-propene(Preparation Example 1), to obtain the title compound (1.2g, yield 60-95%).

Ή NMR(400MHz, CDC1 ₃ ) 60.89~0.93(m, 3H), 1.30~1.39(m, 2H), 1.49~1.52(m, 2H), 1.56~1.62(m, 2H), 2.05(d, J=5.2Hz, 1H), 2.74(d, J=5.2Hz, 1H), 3.72~3.77(m, 1H), 4.98(t, J=4.8Hz, 1H), 7.28~7.50(m, 3H)

Preparation Example 37: Synthesis of the mixture of l-(2,4-dichlorophenyl)- (S,S)-l,2-hexanediol and l-(2,4-dichlorophenyl)-(R,R)-l,2-hexanediol

The substantially same method as described in Preparation Example 16 was conducted, except that l-(2,4-dichlorophenyl)-trans-l-hexene(Preparation Example 8) was used instead of l-(2-chlorophenyl)-trans-l-propene(Preparation Example 1), to obtain the title compound (0.67g, yield 60-95%).

Ή NMR(400MHz, CDC1 ₃ ) 60.89~0.93(m, 3H), 1.30~1.39(m, 2H), 1.49-1.52(m, 2H), 1.56-1.62(m, 2H), 2.05(d, J=5.2Hz, 1H), 2.74(d, J=5.2Hz, 1H), 3.72~3.77(m, 1 H), 4.98(t, J=4.8Hz, 1H), 7.28~7.50(m, 3H)

Preparation Example 38: Synthesis of l-(2,6-dichlorophenyl)-(S,S)-l,2- propanediol

The substantially same method as described in Preparation Example 14 was conducted, except that l -(2,6-dichlorophenyl)-trans-l-propene(Preparation Example 9) was used instead of l-(2-chlorophenyl)-trans-l-propene(Preparation Example 1), to obtain the title compound (0.9g, yield 60-90%). Ή NMR(400MHz, CDC1 ₃ ) 51.10(d, J=6.4Hz, 3H), 2.72(d, J=2.4Hz, 1H), 3.10(d, J=8.4Hz, 1H), 4.47~4.54(m, 1H), 5.24(t, J=8.8Hz, 1H), 7.18~7.36(m, 3H)

Preparation Example 39: Synthesis of l-(2,6-dichlorophenyl)-(R,R)-l,2- propanediol

The substantially same method as described in Preparation Example 15 was conducted, except that l -(2,6-dichlorophenyl)-trans-l -propene(Preparation Example 9) was used instead of l-(2-chlorophenyl)-trans-l-propene(Preparation Example 1), to obtain the title compound (0.84g, yield 60-90%).

Ή NMR(400MHz, CDC1 ₃ ) 61.10(d, J=6.4Hz, 3H), 2.72(d, J=2.4Hz, 1H), 3.10(d, J=8.4Hz, 1 H), 4.47~4.54(m, 1H), 5.24(t, J=8.8Hz, 1 H), 7.18~7.36(m, 3H)

Preparation Example 40: Synthesis of the mixture of l-(2,6-dichlorophenyl)- (S,S)-l,2-propanediol and !-(2,6-dichlorophenyI)-(R,R)-l,2-propanedioI

The substantially same method as described in Preparation Example 16 was conducted, except that l-(2,6-dichlorophenyl)-trans-l-propene(Preparation Example 9) was used instead of l-(2-chlorophenyl)-trans- l-propene(Preparation Example 1), to obtain the title compound (0.91 g, yield 60-90%).

Ή NMR(400MHz, CDCI ₃ ) 51.10(d, J=6.4Hz, 3H), 2.72(d, J=2.4Hz, 1 H), 3.10(d, J=8.4Hz, 1H), 4.47~4.54(m, 1H), 5.24(t, J=8.8Hz, 1 H), 7.18~7.36(m, 3H)

Preparation Example 41: Synthesis of l-(2,6-dichlorophenyl)-(S,S)-1.2- butanediol

The substantially same method as described in Preparation Example 14 was conducted, except that l -(2,6-dichlorophenyl)-trans-l-butene(Preparation Example 10) was used instead of l-(2-chlorophenyl)-trans-l-propene(Preparation Example 1 ), to obtain the title compound ( 1.23g, yield 60-95%).

Ή NMR(400MHz, CDC1 ₃ ) 50.97(t, J=7.6Hz, 3H), 1.26~1.53(m, 2H), 2.64(dd, J=0.8Hz, J=4.0Hz, 1 H), 3.14(d, J=8.4Hz, 1H), 4.22~4.26(m, 1H), 5.26(t, J=8.4Hz, 1 H), 7.17~7.35(m, 3H)

Preparation Example 42: Synthesis of l-(2,6-dichlorophenyl)-(R,R)-l,2- butanediol

The substantially same method as described in Preparation Example 15 was conducted, except that l -(2,6-dichlorophenyl)-trans-l-butene(Preparation Example 10) was used instead of l-(2-chlorophenyl)-trans-l-propene(Preparation Example 1), to obtain the title compound (0.96g, yield 60-95%).

Ή NMR(400MHz, CDC1 ₃ ) 50.97(t, J=7.6Hz, 3H), 1.26-1.53(m, 2H), 2.64(dd,

J=0.8Hz, J=4.0Hz, 1 H), 3.14(d, J=8.4Hz, 1H), 4.22~4.26(m, 1 H), 5.26(t, J=8.4Hz, 1 H), 7.17~7.35(m, 3H)

Preparation Example 43: Synthesis of the mixture of l-(2,6-dichIorophenyl)- (S,S)-l,2-butanediol and l-(2,6-dichlorophenyl)-(R,R)-l,2-butanediol

The substantially same method as described in Preparation Example 16 was conducted, except that l-(2,6-dichlorophenyl)-trans-l-butene(Preparation Example 10) was used instead of l-(2-chlorophenyl)-trans-l-propene(Preparation Example 1 ), to obtain the title compound (0.86g, yield 60-95%).

Ή NMR(400MHz, CDC1 ₃ ) 60.97(t, J=7.6Hz, 3H), 1.26~1.53(m, 2H), 2.64(dd, J=0.8Hz, J=4.0Hz, 1H), 3.14(d, J=8.4Hz, 1H), 4.22~4.26(m, 1H), 5.26(t, J=8.4Hz, 1H), 7.17-7.35(m, 3H) Preparation Example 44: Synthesis of l-(2,6-dichlorophenyl)-3-methyl-(S,S)-l,2- butanediol

The substantially same method as described in Preparation Example 14 was conducted, except that 1 -(2, 6-dichlorophenyl)-3 -methyl-trans- l-butene(Preparation Example 11) was used instead of l-(2-chlorophenyl)-trans-l-propene(Preparation Example 1), to obtain the title compound (0.25g, yield 60~95%).

Ή NMR(400MHz, CDC1 ₃ ) 51.00(d, J=6.8Hz, 6H), 1.60~1.65(m, 1H), 2.35(d, J=4.0Hz, 1H), 3.12(d, J=8.4Hz, 1H), 4.13~4.18(m, 1H), 5.36(t, J=7.6Hz, 1H), 7.l7~7.35(m, 3H)

Preparation Example 45: Synthesis of l-(2,6-dichIorophenyl)-3-methyl-(R,R)- 1,2-butanediol

The substantially same method as described in Preparation Example 15 was conducted, except that l -(2,6-dichlorophenyl)-3-methyl-trans-l-butene(Preparation Example 1 1) was used instead of l -(2-chlorophenyl)-trans-l-propene(Preparation Example 1), to obtain the title compound (0.37g, yield 60-95%).

Ή NMR(400MHz, CDC1 ₃ ) 51.00(d, J=6.8Hz, 6H), 1.60~1.65(m, l H), 2.35(d, J=4.0Hz, 1H), 3.12(d, J=8.4Hz, 1H), 4.13~4.18(m, 1H), 5.36(t, J=7.6Hz, 1H), 7.17~7.35(m, 3H)

Preparation Example 46: Synthesis of the mixture of l-(2,6-dichlorophenyl)-3- methyl-(S,S)-l,2-butanediol and l-(2,6-dichlorophenyl)-3-methyl-(R,R)-l,2-butanediol

The substantially same method as described in Preparation Example 16 was conducted, except that l -(2,6-dichlorophenyl)-3-methyl-trans-l-butene(Preparation Example 1 1) was used instead of l-(2-chlorophenyl)-trans-l-propene(Preparation Example 1), to obtain the title compound (0.47g, yield 60-95%).

Ή NMR(400MHz, CDC1 ₃ ) 61.00(d, J=6.8Hz, 6H), 1.60~1.65(m, 1H), 2.35(d, J=4.0Hz, 1 H), 3.12(d, J=8.4Hz, 1H), 4.13~4.18(m, 1H), 5.36(t, J=7.6Hz, 1H), 7.17~7.35(m, 3H)

Preparation Example 47: Synthesis of l-(2,6-dichlorophenyi)-(S,S)-l,2- hexanediol

The substantially same method as described in Preparation Example 14 was conducted, except that l -(2,6-dichlorophenyl)-trans-l -hexene(Preparation Example 12) was used instead of l -(2-chlorophenyl)-trans-l-propene(Preparation Example 1), to obtain the title compound (0.36g, yield 60-90%).

Ή NMR(400MHz, CDC1 ₃ ) 60.85(t, J=6.8Hz, 3H), 1.20-1.3 l(m, 4H), 1.45-1.53(m, 2H), 2.61~2.62(m, 1H), 3.12(d, J=8.4Hz, 1 H), 4.28~4.33(m, 1H), 5.25(t, J=8.4Hz, 1 H), 7.18~7.35(m, 3H)

Preparation Example 48: Synthesis of l-(2,6-dichlorophenyl)-(R,R)-l,2- hexanediol

The substantially same method as described in Preparation Example 15 was conducted, except that l -(2,6-dichlorophenyl)-trans-l -hexene(Preparation Example 12) was used instead of l-(2-chlorophenyl)-trans-l-propene(Preparation Example 1), to obtain the title compound (0.58g, yield 60-90%).

Ή NMR(400MHz, CDC1 ₃ ) 60.85(t, J=6.8Hz, 3H), 1.20-1.3 l(m, 4H), 1.45~1.53(m, 2H), 2.61-2.62(m, l H), 3.12(d, J=8.4Hz, 1H), 4.28~4.33(m, 1H), 5.25(t, J=8.4Hz, 1 H), 7.18~7.35(m, 3H)

Preparation Example 49: Synthesis of the mixture of l-(2,6-dichlorophenyl)- (S,S)-l,2-hexanediol and l-(2,6-dichlorophenyl)-(R,R)-l,2-hexanediol

The substantially same method as described in Preparation Example 16 was conducted, except that l -(2,6-dichlorophenyl)-trans-l-hexene(Preparation Example 12) was used instead of l-(2-chlorophenyl)-trans- l-propene(Preparation Example 1), to obtain the title compound (0.62g, yield 60-90%).

Ή NMR(400MHz, CDC1 ₃ ) 60.85(t, J=6.8Hz, 3H), 1.20-1.3 l (m, 4H), 1.45~1.53(m, 2H), 2.61~2.62(m, 1 H), 3.12(d, J=8.4Hz, 1H), 4.28~4.33(m, lH), 5.25(t, J=8.4Hz, 1H), 7.18~7.35(m, 3H)

Preparation Example 50: Synthesis of methyl 2-(2-chlorophenyl)-(R)-2» hydroxyacetate

15g of (R)-2-chloromandelic acid was mixed with methanol (CH ₃ OH, 150ml) and phosphorus chloride oxide (POCl ₃ , 0.76ml) in a flask by stirring using a magnetic stirrer at the room temperature for 6 hours. When the reaction was completed, the obtained product was washed with an aqueous solution of sodium sulfite (Na ₂ S0 ₃ ) and ethylacetate (EA). Then, the organic layer was dehydrated with anhydrous magnesium sulfate (MgSC^), filtrated, and concented under reduced pressure. The concentrated residue was purified by a silica gel column chromatography to produce the title compound (15.64g, yield 95%).

Ή NMR(400MHz, CDC1 ₃ ) δ 3.59(d, J=5.2, 1H), 3.79(t, J=6.0, 3H), 5.59(d, J=5.2, 1 H), 7.28~7.43(m, 4H)

Preparation Example 51: Synthesis of 2-(2-chlorophenyl)-(R)-2-hydroxy-N- methoxy-N-methylacetamide

Ν,Ο-dimethylhydroxylamine hydrochloride (Ν,Ο-dimethylhydroxylamine.HCl, 15.2g) was dissolved in dichloromethane (DCM, 150ml), and cooled to 0 ^° C using an ice- bath. Then, 77.7ml of 2.0M trimethylaluminium in hexane was slowly added thereto in drop-wise manner for 30 minutes. Thereafter, the ice-bath was removed, and the obtained product was stirred at the room temperature for 2 hours. Methyl-2-(2-chlorophenyl)-(R)-2- hydroxyacetate(15.64g) dissolved in dichloromethane(DCM, 150ml) was added in drop-wise manner thereto at the room temperature for 30 minutes, and subjected to reflux for 12 hours. When the reaction was completed, the obtained product was cooled to 0 ^° C , and washed by a slow drop-wise addition of hydrochloric acid (HC1, 200ml). The obtained organic layer was washed with distilled water and brine, dehydrated with anhydrous magnesium sulfate (MgS0 ₄ ), filtrated, and concented under reduced pressure. The concentrated residue was purified by a silica gel column chromatography to produce the title compound (14.68g, yield 82%).

Ή NMR(400MHz, CDC1 ₃ ) 53.23(s, 3H), 3.28(s, 3H), 4.33(d, J=6.0Hz, 1H), 5.81 (d, J=5.6Hz, 1H), 7.23~7.42(m, 4H)

Preparation Example 52: Synthesis of 2-(2-chlorophenyl)-N-metho\y-(R)- butyl dimethlysiloxy)-N-methylacetamide

2-(2-chlorophenyl)-(R)-2-hydroxy-N-methoxy-N-methylacetamide (0.81 g,

3.52mmol) obtained in Preparation Example 51 was dissolved in dichloromethane (DCM), and cooled to 0 ^° C . Imedazole (0.36g, 5.28mmol) was slowly added, and stirred. TBDMS-Cl (t-butyldimethylsily chloride, 0.79g, 5.28mmol) was slowly added. When the reaction was completed, the reaction mixture was quenched with H ₂ 0. The organic layer was separated and collected. The aqueous layer was extracted with CH ₂ C1 ₂ (300mL), dried over MgS0 ₄ . Concentration under vacuum provided a title compound. (0.97g, 80~95%).

Ή NMR(400MHz, CDC1 ₃ ) 5-0.03(s, 3H), 0.14(s, 3H), 0.94(s, 9H), 2.97(s, 3H), 3.02(s, 3H), 5.83(s, 1 H), 7.25~7.60(m, 4H)

Preparation Example 53: Synthesis of I-(2-chlorophenyl)-(R)-l-(t- butyldimethyl-siloxy)propane-2-on S

2-(2-chlorophenyl)-N-methoxy-(R)-2-(t-butyldimethylsiloxy)-N - methylacetamide(0.9g) obtained in Preparation Example 52 was dissolved in tetrahydrofuran(THF), and cooled to 0 ^° C . 3.0M methyl magnesium bromide (MeMgBr, 2.18ml) solution in ether was added thereto in drop-wise manner for 30 minutes, and the obtained product was stirred at 0 ^° C . When the reaction was completed, diefhylether was added thereto. The obtained product was washed with 10%(w/v) potassium hydrogen sulfate ( HSO _4, 100ml) and then, washed again with brine. The obtained organic layer was dehydrated with anhydrous magnesium sulfate (MgS0 ₄ ), filtrated, and concentrated under reduced, pressure. The concentrated residue was purified by a silica gel column chromatography to produce the title compound (0.69g, yield 85~95%).

Ή NMR(400MHz, CDC1 ₃ ) 5-0.3(s, 3H), 0.14(s, 3H), 0.94(s, 9H), 2.18(s, 3H), 5.50(s, 1H), 7.27~7.56(m, 4H)

Preparation Example 54: Synthesis of l-(2-chlorophenyl)-(R)-l-(t- butyldimethyl-siloxy)-(S)-2-propanol

1 -(2-chlorophenyl)-(R)- 1 -(t-butyldimethyl-siloxy)propane-2-on(0.14g) obtained in Preparation Example 53 was dissolved in ether, and cooled to -78 ^° C . Zinc borohydride(Zn(B 1-14) ₂ ) was slowly added thereto and the obtained product was stirred. When the reaction was completed, the obtained product was washed by H ₂ 0. The obtained organic layer was washed with H ₂ 0, dehydrated with anhydrous magnesium sulfate (MgSC^), filtrated, and concentrated under reduced pressure. The concentrated residue was purified by a silica gel column chromatography to produce the title compound (0.04g, yield 25~33%, cis : trans = 2 : 1).

Ή NMR(400MHz, CDC1 ₃ ) 6-0.11(s, 3H), 0.11 (s, 3H), 0.93(S, 9H), 1.07(d, J=6.4 3H), 2.05(d, J=6.4 1H), 4.01~4.05(m, 1H), 5.18(d, J=4.0, 1H), 7.20~7.56(m, 4H))

Preparation Example 55: Synthesis of l-(2-chlorophenyi)-(R,S)-l,2- propanediol

l-(2-chlorophenyl)-(R)-l-(t-butyldimethyl-siloxy)-(S)-2-prop anol(10.38g) obtained in Preparation Example 54 was dissolved in methanol (CH ₃ OH, 100ml), and then, cooled to 0 ^° C . 8M hydrochloric acid(HCl, 56.2ml) was slowly added in drop-wise manner to the obtained product, and then, the obtained product was warmed to the room temperature, and stirred for 15 hours. When the reaction was completed, the obtained product was cooled to 0 ^° C . 5N sodium hydroxide (NaOH, 30ml) was slowly added thereto, and the obtained product was subjected to vacuum concentration. _m The obtained product was diluted with ethyl acetate. The obtained organic layer was washed with distilled water, dehydrated with anhydrous magnesium sulfate (MgS0 ₄ ), filtrated, and concented under reduced pressure. The concentrated residue was purified by a silica gel column chromatography to produce the title compound (7.05g, yield 60-90%).

Ή NMR(400MHz, CDCI ₃ ) 61.07(d, J=6.8, 3H), 2.01(d, J=5.6, 1H), 2.61 (s, 1H), 4.21~4.27(m, l H), 5.24(d, J=3.6, 1H), 7.22~7.64(m, 4H)

Preparation Example 56: Synthesis of l-(2-chlorophenyl)-(S,R)-l,2-propanediol

The substantially same method as described in Preparation Example 50-55 was conducted, except that (S)-2-chloromandelic acid was used instead of (R)-2-chloromandelic acid, to obtain the title compound (5.04g, yield 84%).

Ή NMR(400MHz, CDCI3) 61.07(d, J=6.8, 3H), 2.00(d, J=5.6, 1H), 2.54(d, J=3.6, 1H), 4.22~4.26(m, 1H), 5.25(t, J=3.2, 1H), 7.22~7.65(m, 4H) Preparation Example 57: Synthesis of l-(2,3-dichlorophenyl)-(S,S)-l,2- propanediol The substantially same method as described in Preparation Example 14 was conducted, except that l -(2,3-dichlorophenyl)-trans-l-propene(Preparation Example 13) was used instead of l -(2-chlorophenyl)-trans-l -propene(Preparation Example 1 ), to obtain the title compound (0.9g, yield 60-90%).

Ή NMR(400MHz, CDC1 ₃ ) 81.10(d, J=6.4Hz, 3H), 2.72(d, J=2.4Hz, 1 H), 3.10(d, J=8.4Hz, 1 H), 4.47~4.54(m, 1H), 5.24(t, J=8.8Hz, 1H), 7.18- (m, 3H)

Preparation Example 58: Synthesis of l-(2,3-dichlorophenyl)-(R,R)-l,2- propanediol

The substantially same method as described in Preparation Example 15 was conducted, except that l -(2,3-dichlorophenyl)-trans-l -propene(Preparation Example 13) was used instead of l -(2-chlorophenyl)-trans- l -propene(Preparation Example 1 ), to obtain the title compound (0.84g, yield 60-90%).

!H NMR(400MHz, CDC1 ₃ ) 81.10(d, J=6.4Hz, 3H), 2.72(d, J=2.4Hz, 1H)„ 3.10(d, J=8.4Hz, l H), 4.47-4.54(m, 1 H), 5.24(t, J=8.8Hz, 1 H), 7.18- (m, 3H)

Preparation Example 59: Synthesis of the mixture of l-(2,3-dichlorophenyl)- (S,S)-l,2-propanediol and l-(2,3-dichlorophenyl)-(R,R)-l,2-propanediol

The substantially same method as described in Preparation Example 16 was conducted, except that l -(2,3-dichlorophenyl)-trans-l -propene(Preparation Example 13) was used instead of l -(2-chlorophenyl)-trans- l -propene(Preparation Example 1), to obtain the title compound (0.91 g, yield 60-90%).

Ή NMR(400MHz, CDC1 ₃ ) 61 .10(d, J=6.4Hz, 3H), 2.72(d, J=2.4Hz, 1 H), 3.10(d, J=8.4Hz, 1H), 4.47~4.54(m, 1 H), 5.24(t, J=8.8Hz, 1 H), 7.18~(m, 3H)

Preparation Example 60: Synthesis of l-(2-fluorophenyl)-trans-l-propene

The substantially same method as described in Preparation Example 1 was conducted, except that 2-fluorobenzenaldehyde was used instead of 2-chlorobenzenealdehyde, to obtain the title compound (6.67g, yield 61 %).

Ή NMR(400MHz, CDC1 ₃ ) 51.94(d, J=6.8Hz, 3H), 6.30~6.38(m, 1 H), 6.57(d,

J=16Hz, 1 H), 7.00-7.41 (m, 4H)

Preparation Example 61: Synthesis of l-(2-fluorophenyi)-(S,S)-l,2-propanediol

The substantially same method as described in Preparation Example 14 was conducted, except that l -(2-fluorophenyl)-trans- l -propene (Preparation Example 60) was used instead of l-(2-chlorophenyl)-trans- l -propene (Preparation Example 1), to obtain the title compound (6.46g, yield 78%).

Ή NMR(400MHz, CDC1 ₃ ) 81, 15(d, J=6.4Hz, 3H), 2.43(d, J=3.6Hz, l H), 2.69(d, J=4.8Hz, 1H), 3.90~3.98(m, 1 H), 4.78(dd, J=4.4, 7.2Hz, 1 H), 7.04~7.50(m, 4H)

Preparation Example 62: Synthesis of l-(2-fluorophenyl)-(R,R)-l,2-propanediol

The substantially same method as described in Preparation Example 15 was conducted, except that 1 -(2-fluorophenyl)-trans- 1 -propene (Preparation Example 60) was used instead of l -(2-chlorophenyl)-trans-l -propene (Preparation Example 1 ), to obtain the title compound (3.29g, yield 79%).

Ή NMR(400MHz, CDC1 ₃ ) 51.15(d, J=6.4Hz, 3H), 2.43(d, J=3.6Hz, 1 H), 2.69(d, J=4.8Hz, 1 H), 3.90~3.98(m, 1 H), 4.78(dd, J=4.4, 7.2Hz, 1H), 7.04~7.50(m, 4H)

Preparation Example 63: Synthesis of 2-iodobenzenealdehyde

In a flask, 2-iodobenzyl alcohol (4g, 17.09mmol) was dissolved in dichloromethane (MC, 85ml), and then, manganese oxide (Mn0 ₂ , 14.86g, 170.92mmol) was added thereto. The obtained reaction product was stirred under the reflux condition. When the reaction was completed, the obtained reaction product was cooled to the room temperature, and then, fiteated and concentrated using celite, to obtain the title compound (3.6g, yield 91 %).

Ή NMR(400MHz, CDCl ₃ )57.30~7.99(m, 4H), 10.10(s, 1 H)

Preparation Example 64: Synthesis of l-(2-iodophenyl)-trans-l-propene

The substantially same method as described in Preparation Example 1 was conducted, except that 2-iodobenzenealdehyde (Preparation Example 63) was used instead of 2- chlorobenzenealdehyde, to obtain the title compound (3.4g, yield 65%).

Ή NMR(400MHz, CDCl ₃ )61.95(dd, J=6.8Hz, 1.6Hz, 3H), 6.09-6.18(m, 1 H), 6.60(dd, J=l 5.66Hz, 1 .8 Hz, lH), 6.89~7.84(m, 4H)

Preparation Example 65: Synthesis of l-(2-iodophenyl)-trans-l-butene

The substantially same method as described in Preparation Example 64 was conducted, except that 3-heptanone was used instead of 3-pentanone, to obtain the title compound (8.5g, yield 75%).

Ή NMR(400MHz, CDCl ₃ )61.46(t, J=7.6Hz, 3H), 2.26~2.34(m, 2H), 6.17(dt, J=15.6Hz, 6.6Hz 1 H), 6.57(d, J=15.6Hz, l H), 6.89~7.85(m, 4H)

Preparation Example 66: Synthesis of l-(2-iodophenyl)-(S,S)-l,2-propanediol The substantially same method as described in Preparation Example 14 was conducted, except that l-(2-iodophenyl)-trans- l-propene (Preparation Example 64) was used instead of l-(2-chlorophenyl)-trans- l-propene (Preparation Example 1), to obtain the title compound (3.4g,. yield 88%).

Ή NMR(400MHz, CDCl ₃ )61.27(d, J=6.4Hz, 3H), 2.26(br s, 1H), 2.74(br s, 1H), 3.99(t, J=6.0Hz, 1H), 4.8 l (d, J=4.0Hz, 1H), 7.01~7.87(m, 4H)

Preparation Example 67: Synthesis of l-(2-iodorophenyl)-(R,R)-l,2-propanediol

The substantially same method as described in Preparation Example 15 was conducted was conducted, except that l-(2-iodophenyl)-trans-l-propene (Preparation Example 64) was used instead of l -(2-chlorophenyl)-trans-l-propene (Preparation Example 1), to obtain the title compound (7.4g, yield 84%).

Ή NMR(400MHz, CDCl ₃ )51.26(d, J=6.4Hz, 3H), 2.35(br s, 1 H), 2.85(br d, J=4.0Hz, 1H), 3.98(t, J=6.2Hz, 1H), 4.80(dd, J=5.0, 4.4Hz, 1 H), 7.00~7.87(m, 4H)

Preparation Example 68: Synthesis of l-(2- iodophenyl)-(S,S)-l,2-butanediol

The substantially same method as described in Preparation Example 14 was conducted was conducted, except that l -(2-iodophenyl)-trans-l -butene (Preparation Example 65) was used instead of l-(2-chlorophenyl)-trans-l-propene (Preparation Example 1), to obtain the title compound (9.5g, yield 84%).

Ή NMR(400MHz, CDCl ₃ )51.04(t, J=7.6Hz, 3H), 1.60-1.71 (m, 2H), 2.07(br s, 1H), 2.74(br s, 1H), 3.71~3.76(m, 1 H), 4.87(d, J=4.8Hz, 1H), 7.01~7.87(m, 4H)

Preparation Example 69 : Preparation of l-(2-chlorophenyl)-(S,S)-l,2-(Bis- trimethylsilanyloxy) propane To a stirred solution of l-(2-chlorophenyl)-(S,S)-l ,2-propanediol(Preparation exampleM, 67g, 0.35mol) in CH ₂ C1 ₂ (670ml) was added Et ₃ N (200mL, 1.43mol) and TMSCl

(113.9mL, 0.89mol) at 0°C under N ₂ . The reaction mixture was allowed to stir at 0°C for 3hr.

The reaction mixture was quenched with H ₂ 0 (650mL) at 0°C. The organic layer was separated and collected. The aqueous layer was extracted with CH ₂ C1 ₂ (300mL), dried over MgS0 ₄ . Concentration under vacuum provided a crude product. 104.18g (117.44%).

Ή NMR(400MHz, CDCl ₃ )5-0.053(s, 9H), 0.044(s, 9H), 1.15(d, J=5.6Hz, 3H), 3.977~3.918(m, 1 H), 4.973(d, J=6.4Hz, 1H), 7.207~7.165(m,lH), 7.321~7.245(m, 2H), 7.566~7.543(m, 1H)

Preparation Example 70 : Preparation of l-(2-chlorophenyl)-(R,R)-l,2-(Bis- trimethylsilanyloxy) propane

The substantially same method as described in Preparation Example 69 was conducted, except that l-(2-chlorophenyl)-(R,R)-l,2-propanediol(Preparation examplel 5)was used instead of l-(2-chlorophenyl)-(S,S)-l,2-propanediol(Preparation exampleM) to obtain the title compound (8.5g, yield 90-120%).

Ή NMR(400MHz, CDCl ₃ )8-0.053(s, 9H), 0.044(s, 9H), 1.15(d, J=5.6Hz, 3H), 3.977~3.918(m, 1H), 4.973(d, J=6.4Hz, 1H), 7.21~7.54(m,4H)

Preparation Example 71 : Preparation of l-(2-chlorophenyl)— l,2-(Bis- trimethylsilanyloxy) propane

The substantially same method as described in Preparation Example 69 was conducted, except that l-(2-chlorophenyl)propane- l ,2-diol(Preparation examplel6)was used instead of l-(2-chlorophenyl)-(S,S)- l,2-propanediol(Preparation exampleH) to obtain the title compound (5.2g, yield 90-120%). Ή NMR(400 Hz, CDCl ₃ )5-0.053(s, 9H), 0.044(s, 9H), 1.15(d, J=5.6Hz, 3H), 3.977-3.918(m, 1H), 4.973(d, J6.4Hz, 1H), 7.21~7.54(m,4H)

Preparation Example 72 : Preparation of l-(2-chlorophenyl)-(S,R)-l,2-(Bis- trimethylsilanyloxy) propane

The substantially same method as described in Preparation Example 69 was conducted, except that l-(2-chlorophenyl)-(S,R)-l ,2-propanediol(Preparation example56)was used instead of l-(2-chlorophenyl)-(S,S)-l,2-propanediol(Preparation example 14) to obtain the title compound (3.4g, yield 90-120%).

Ή NMR(400MHz, CDCl ₃ )5-0.053(s, 9H), 0.044(s, 9H), 1.15(d, J=5.6Hz, 3H),

3.977~3.918(m, 1H), 4.973(d, J=6.4Hz, 1H), 7.21~7.54(m,4H)

Preparation Example 73 : Preparation of l-(2-chlorophenyl)-(R,S)-l,2-(Bis- trimethylsilanyloxy) propane

The substantially same method as described in Preparation Example 69 was conducted, except that l-(2-chlorophenyl)-(R,S)-l ,2-propanediol(Preparation example55)was used instead of l-(2-chlorophenyl)-(S,S)-l,2-propanediol(Preparation example 14) to obtain the title compound (3.2g, yield 90-120%).

Ή NMR(400MHz, CDCl ₃ )6-0.053(s, 9H), 0.044(s, 9H), 1.15(d, J=5.6Hz, 3H), 3.977-3.918(m, 1 H), 4.973(d, J=6.4Hz, 1H), 7.21~7.54(m,4H)

Preparation Example 74 : Preparation of l-(2-chlorophenyl)-(S,S)-l,2-(Bis- trimethylsilanyloxy) butane

The substantially same method as described in Preparation Example 69 was conducted, except that l-(2-chlorophenyl)-(S,S)-l ,2-butanediol(Preparation example 17)was used instead of l-(2-chlorophenyl)-(S,S)-l,2-propanediol(Preparation examplel4) to obtain the title compound (3.6g, yield 90-120%).

Ή NMR(400MHz, CDCl ₃ )6-0.053(s, 9H), 0.044(s, 9H), 1.01 (t, J=7.4Hz, 3H), 1.52~1.65(m, 2H), 3.69~3.75(m, 1H), 5.05(t, J=5.0Hz, l H), 7.23~7.54(m,4H)

Preparation Example 75 : Preparation of l-(2-chlorophenyl)-(R,R)-l,2-(Bis- trimethylsilanyloxy) butane

The substantially same method as described in Preparation Example 69 was conducted, except that l -(2-chlorophenyl)-(R,R)-l ,2-butanediol(Preparation examplel 8)was used instead of l-(2-chlorophenyl)-(S,S)-l,2-propanediol(Preparation examplel4) to obtain the title compound (3.5g, yield 90-120%).

Ή NMR(400MHz, CDCl ₃ )6-0.053(s, 9H), 0.044(s, 9H), 1.01(t, J=7.4Hz, 3H), 1.52-1.65(m, 2H), 3.69~3.75(m, 1H), 5.05(t, J=5.0Hz, 1H), 7.23~7.54(m,4H)

Preparation Example 76 : Preparation of l-(2-chlorophenyi)-l,2-(Bis- trimethylsilanyloxy) butane

The substantially same method as described in Preparation Example 69 was conducted, except that l-(2-chlorophenyl)-l ,2-butanediol(Preparation examplel9)was used instead of l-(2-chlorophenyl)-(S,S)-l ,2-propanediol(Preparation example 14) to obtain the title compound (3. Og, yield 90-120%).

Ή NMR(400MHz, CDCl ₃ )5-0.053(s, 9H), 0.044(s, 9H), 1.01 (t, J=7.4Hz, 3H), 1.52~1.65(m, 2H), 3.69~3.75(m, 1 H), 5.05(t, J=5.0Hz, 1H), 7.23~7.54(m,4H)

Preparation Example 77 : Preparation of l-(2-chlorophenyl)-3-methyl-(S,S)- l,2-(Bis-trimethylsilanyloxy)-butane OTMS

OTMS

The substantially same method as described in Preparation Example 69 was conducted, except that l-(2-chlorophenyl)-3-methyl-(S,S)-l ,2-butanediol(Preparation example20)was used instead of l-(2-chlorophenyl)-(S,S)-l,2-propanediol(Preparation exampleH) to obtain the title (2.7g, yield 90-120%).

Ή NMR(400MHz, CDCl ₃ )6-0.053(s, 9H), 0.044(s, 9H), 1.07(t, J=7.2Hz, 6H), 1.83~1.89(m, 1H), 3.53~3.56(m, 1H), 5.22~5.25(m, 1H), 7.23~7.55(m,4H)

Preparation Example 78 : Preparation of l-(2-chlorophenyl)-3-methyI-(R,R)- l,2-(Bis-trimethylsilanyloxy)-butane

The substantially same method as described in Preparation Example 69 was conducted, except that l-(2-chlorophenyl)-3-methyl-(R,R)-l ,2-butanediol(Preparation example21 )was used instead of l-(2-chlorophenyl)-(S,S)-l,2-propanediol(Preparation exampleH) to obtain the title compound (2.4g, yield 90-120%).

Ή NMRHOOMHz, CDCl ₃ )5-0.053(s, 9H), 0.044(s, 9H), 1.07(t, J=7.2Hz, 6H), 1.83~1.89(m, 1H), 3.53~3.56(m, IH), 5.22~5.25(m, 1H), 7.23~7.55(m,4H)

Preparation Example 79 : Preparation of l-(2-chlorophenyl)-3-methyl-l,2- (Bis-trimethylsilanyloxy)-butane

_C l OTMS

The substantially same method as described in Preparation Example 69 was conducted, except that l-(2-chlorophenyl)-3-methyl- l,2-butanediol(Preparation example22)was used instead of l-(2-chlorophenyl)-(S,S)-l ,2-propanediol(Preparation exampleH) to obtain the title compound (2.8g, yield 90-120%).

Ή NMR(400MHz, CDCl ₃ )5-0.053(s, 9H), 0.044(s, 9H), 1.07(t, J=7.2Hz, 6H), 1.83-1.89(m, I H), 3.53-3.56(m, 1H), 5.22~5.25(m, IH), 7.23~7.55(m,4H) Preparation Example 80 : Preparation of l-(2-chlorophenyl)-(S,S)-l,2-(Bis- trimethyIsilanyloxy)-hexane

The substantially same method as described in Preparation Example 69 was conducted, except that l -(2-chlorophenyl)-(S,S)-l,2-hexanediol(Preparation example23)was used instead of l-(2-chlorophenyl)-(S,S)-l ,2-propanediol(Preparation examplel4) to obtain the title compound (3. lg, yield 90-120%).

Ή NMR(400MHz, CDCl ₃ )5-0.053(s, 9H), 0.044(s, 9H), 0.90(t, J=7.2Hz, 3H), 1.35~1.65(m, 6H), 3.78~3.83(m, l H), 5.04(t, J=5.0Hz, lH), 7.23~7.53(m,4H)

Preparation Example 81 : Preparation of l-(2-chlorophenyl)-(S,S)-l,2-(Bis- trimethylsilanyloxy)-hexane

The substantially same method as described in Preparation Example 69 was conducted, except that l-(2-chlorophenyl)-(R,R)-l,2-hexanediol(Preparation example24)was used instead of l-(2-chlorophenyl)-(S,S)-l,2-propanediol(Preparation examplel4) to obtain the title compound (3.3g, yield 90-120%).

'H . NMR(400MHz, CDCl ₃ )5-0.053(s, 9H), 0.044(s, 9H), 0.90(t, J=7.2Hz, 3H), 1.35~1.65(m, 6H), 3.78~3.83(m, 1H), 5.04(t, J=5.0Hz, 1 H), 7.23~7.53(m,4H)

Preparation Example 82 : Preparation of l-(2-chlorophenyl)-(S,S)-l,2-(Bis- trimethylsilanyloxy)-hexane

The substantially same method as described in Preparation Example 69 was conducted, except that l-(2-chlorophenyl)-l ,2-hexanediol(Preparation example25)was used instead of l-(2-chlorophenyl)-(S,S)-l,2-propanediol(Preparation exampleH) to obtain the title compound (3.2g, yield 90-120%).

Ή NMR(400MHz, CDCl ₃ )5-0.053(s, 9H), 0.044(s, 9H), 0.90(t, J=7.2Hz, 3H), 1.35~1.65(m, 6H), 3.78~3.83(m, IH), 5.04(t, J=5.0Hz, IH), 7.23~7.53(m,4H)

Preparation Example 83 : Preparation of l-(2,4-dichlorophenyl)-(S,S)-l,2- (Bis-trimethylsilanyloxy)-propane

The substantially same method as described in Preparation Example 69 was conducted, except that l -(2,4-dichlorophenyl)-(S,S)-l ,2-propanediol(Preparation example26)was used instead of l-(2-chlorophenyl)-(S,S)-l ,2-propanediol(Preparation example 14) to obtain the title compound (2.4g, yield 90-120%).

Ή NMR(400MHz, CDCl ₃ )6-0.053(s, 9H), 0.044(s, 9H), l.22(d, J=6.4Hz, 3H), 3.90~3.95(m, IH), 4.94(t, J=5.0Hz, I H), 7.31 (dd, J=2.0Hz, J=8.0Hz, I H), 7.40(d, J=2.0Hz, IH), 7.49(d, J=8.4Hz, IH)

Preparation Example 84 : Preparation of l-(2,6-dichlorophenyl)-(S,S)-l,2- (Bis-trimethylsilanyloxy)-propane

The substantially same method as described in Preparation Example 69 was conducted, except that l-(2,6-dichlorophenyl)-(S,S)-l ,2-propanediol(Preparation example38)was used instead of l-(2-chlorophenyl)-(S,S)- l,2-propanediol(Preparation examplel4) to obtain the title compound (3.4g, yield 90-120%).

Ή NMR(400MHz, CDCl ₃ )6-0.053(s, 9H), 0.044(s, 9H), 1.10(d, J=6.4Hz, 3H), 4.47~4.54(m, IH), 5.24(t, J=8.8Hz, IH), 7.13~7.36(m, 3H)

Preparation Example 85 : Preparation of l-(2,3-dichIorophenyl)-(S,S)-l,2- (Bis-trimethylsilanyloxy)-propane The substantially same method as described in Preparation Example 69 was conducted, except that l-(2,3-dichlorophenyl)-(S,S)-l,2-propanediol(Preparation example57)was used instead of l-(2-chlorophenyl)-(S,S)-l ,2-propanediol(Preparation examplel4) to obtain the title compound (2.2g, yield 90-120%).

Ή NMR(400MHz, CDCl ₃ )6-0.053(s, 9H), 0.044(s, 9H), 1.10(d, J=6.4Hz, 3H,), 4.47~4.54(m, 1 H), 5.24(t, J=8.8Hz, l H), 7.18-7.22(m, 3H)

Preparation Example 86 : Preparation of l-(2,4-dichlorophenyl)-(S,S)-l,2- (Bis-trimethylsilanyloxy)-butane

The substantially same method as described in Preparation Example 69 was conducted, except that l-(2,4-dichlorophenyl)-(S,S)-l,2-butanediol(Preparation example29)was used instead of l-(2-chlorophenyl)-(S,S)-l,2-propanediol(Preparation example 14) to obtain the title compound (3.1 g, yield 90-120%).

Ή NMR(400MHz, CDCl ₃ )6-0.053(s, 9H), 0.044(s, 9H), 1.02(t, J=7.4Hz, 3H), 1.54-1.61 (m, 2H>, 3.65-3.68(m, 1H), 5.01(t, J=5.0Hz, 1 H), 7.31~7.49(m, 3H)

Preparation Example 87 : Preparation of l-(2,6-dichlorophenyl)-(S,S)-l,2- (Bis-trimethylsilanyloxy)-butane

The substantially same method as described in Preparation Example 69 was conducted, except that l-(2,6-dichlorophenyl)-(S,S)-l ,2-butanediol(Preparation example41)was used instead of l-(2-chlorophenyl)-(S,S)-l ,2-propanediol(Preparation examplel4) to obtain the title compound (2.8g, yield 90^120%).

Ή NMR(400MHz, CDCl ₃ )5-0.053(s, 9H), 0.044(s, 9H), 0.97(t, J-7.6Hz, 3H), 1.26~1.53(m, 2H), 4.22~4.26(m, 1H), 5.26(t, J=8.4Hz, 1 H), 7.17~7.35(m, 3H)

Preparation Example 88 : Preparation of l-(2,4-dichlorophenyl)-3-methyl- (S,S)- 1 ,2-(Bis-trimethylsilanyloxy)-butane

The substantially same method as described in Preparation Example 69 was conducted, except that l -(2,4-dichlorophenyl)-3-methyl-(S,S)-l ,2-butanediol(Preparation example32)was used instead of l-(2-chlorophenyl)-(S,S)-l ,2-propanediol(Preparation exampleH) to obtain the title compound (2.7g, yield 90-120%).

Ή NMR(400MHz, CDCl ₃ )6-0.053(s, 9H), 0.044(s, 9H), 1.00(d, J=6.8Hz, 6H), 1.60-1.65(m, IH), 4.13-4.18(m, IH), 5.36(t, J=7.6Hz, IH), 7.30~7.53(m, 3H)

Preparation Example 89 : Preparation of l-(2,6-dichlorophenyl)-3-methyI- (S,S)-l,2-(Bis-trimethylsilanyloxy)-butane

The substantially same method as described in Preparation Example 69 was conducted, except that l-(2,6-dichlorophenyl)-3-methyl-(S,S)-l ,2-butanediol(Preparation example44)was used instead of l -(2-chlorophenyl)-(S,S)-l ,2-propanediol(Preparation exampleH) to obtain the title compound (3.3g, yield 90-120%).

Ή NMR(400MHz, CDCl ₃ )5-0.053(s, 9H), 0.044(s, 9H), 1.00(d, J=6.8Hz, 6H), 1.60~1.65(m, l H), 4.13~4.18(m, H), 5.36(t, J=7.6Hz, IH), 7.17~7.35(m, 3H)

Preparation Example 90 : Preparation of l-(2,4-dichlorophenyl)-(S,S)-l,2- (Bis-trimethylsilanyloxy)-hexane

The substantially same method as described in Preparation Example 69 was conducted, except that l-(2,4-dichlorophenyl)-(S,S)-l,2-hexanediol(Preparation example90)was used instead of l-(2-chlorophenyl)-(S,S)-l ,2-propanediol(Preparation example 14) to obtain the title compound (3.6g, yield 90-120%).

Ή NMR(400MHz, CDCl ₃ )6-0.053(s, 9H), 0.044(s, 9H), 0.89~0.93(m, 3H), 1.30~1.39(m, 2H), 1.49~1.52(m, 2H), 1.56-1.6(m, 2H), 3.72~3.77(m, IH), 4.98(t, J=4.8Hz, IH), 7.28~7.50(m, 3H)

Preparation Example 91 : Preparation of l-(2,6-dichlorophenyl)-(S,S)-l,2- (Bis-trimethylsilanyloxy)-hexane

The substantially same method as described in Preparation Example 69 was conducted, except that l-(2,6-dichlorophenyl)-(S,S)-l,2-hexanediol(Preparation example47)was used instead of l-(2-chlorophenyl)-(S,S)-l,2-propanediol(Preparation examplel4) to obtain the title compound (2.8g, yield 90-120%).

Ή NMR(400MHz, CDCl ₃ )5-0.053(s, 9H), 0.044(s, 9H), 0.85(t, J=6.7Hz, 3H), 1.20-1.3 l(m, 4H), 1.45~1.53(m, 2H), 4.28~4.33(m, IH), 5,25(t, J=8.4Hz, IH), 7.18~7.35(m, 3H)

Preparation Example 92 : Preparation of l-(2,4-dichlorophenyl)-(R,R)-l,2- (Bis-trimethylsilanyloxy)-propane

The substantially same method as described in Preparation Example 69 was conducted, except that l-(2,4-dichlorophenyl)-(R,R)-l,2-propanediol(Preparation example27)was used instead of l-(2-chlorophenyl)-(S,S)-l ,2-propanediol(Preparation examplel 4) to obtain the title compound (2.2g, yield 90-120%).

Ή NMR(400MHz, CDCl ₃ )5-0.053(s, 9H), 0.044(s, 9H), 1.22(d, J=6.4Hz, 3H), 3.90~3.95(m, l H), 4.94(t, J=5.0Hz, IH), 7.31~7.49(m, 3H)

Preparation Example 93 : Preparation of l-(2,6-dichlorophenyl)-(R,R)-l,2- (Bis-trimethylsilanyloxy)-propane

The substantially same method as described in Preparation Example 69 was conducted, except that l -(2,6-dichlorophenyl)-(R,R)- l ,2-propanediol(Preparation examples 9)was used instead of l -(2-chlorophenyl)-(S,S)-l ,2-propanediol(Preparation examplel 4) to obtain the title compound (2.6g, yield 90-120%).

Ή NMR(400MHz, CDCl ₃ )5-0.053(s, 9H), 0.044(s, 9H), 1.10(d, J=6.4Hz, 3H), 4.47~4.54(m, 1H), 5.24(t, J=8.8Hz, 1H), 7.18~7.36(m, 3H)

Preparation Example 94 : Preparation of l-(2,3-dichIorophenyl)-(R,R)-l,2- (Bis-trimethylsilanyloxy)-propane

The substantially same method as described in Preparation Example 69 was conducted, except that l-(2,3-dichlorophenyl)-(R,R)-l,2-propanediol(Preparation example58)was used instead of l-(2-chlorophenyl)-(S,S)-l,2-propanediol(Preparation exampleH) to obtain the title compound (2.9g, yield 90-120%).

Ή NMR(400MHz, CDCl )6-0.053(s, 9H), 0.044(s, 9H), 1.10(d, J=6.4Hz, 3H), 4.47~4.54(m, 1H), 5.24(t, J=8.8Hz, 1H), 7.18~7.22(m, 3H)

Preparation Example 95 : Preparation of l-(2,4-dichlorophenyi)-(R,R)-l,2-(Bis- trimethylsilanyloxy)-butane

The substantially same method as described in Preparation Example 69 was conducted, except that l-(2,4-dichlorophenyl)-(R,R)-l ,2-butanediol(Preparation example30)was used instead of l -(2-chlorophenyl)-(S,S)-l ,2-propanediol(Preparation examplel4) to obtain the title compound (3.6g, yield 90-120%).

Ή NMR(400MHz, CDCl ₃ )5-0.053(s, 9H), 0.044(s, 9H), 1.02(t, J=7.4Hz, 3H), 1.54-1.6 l (m, 2H), 3.65~3.68(m, 1H), 5.0 l(t, J=5.0Hz, 1H), 7.31~7.49(m, 3H)

Preparation Example 96 : Preparation of l-(2,6-dichIorophenyl)-(R,R)-l,2- (Bis-trimethylsilanyloxy)-butane

The substantially same method as described in Preparation Example 69 was conducted, except that l-(2,6-dichlorophenyl)-(R,R)-l ,2-butanediol(Preparation example42)was used instead of l-(2-chlorophenyl)-(S,S)- l ,2-propanediol(Preparation examplel4) to obtain the title compound (3.3g, yield 90-120%).

Ή NMR(400MHz, CDCl ₃ )5-0.053(s, 9H), 0.044(s, 9H), 0.97(t, J=7.6Hz, 3H), 1.26~1.53(m, 2H), 4.22~4.26(m, 1H), 5.26(t, J=8.4Hz, 1H), 7.17~7.35(m, 3H)

Preparation Example 97 : Preparation of l-(2,4-dichlorophenyl)-3-methyl- (R,R)-l,2-(Bis-trimethyIsilanyloxy)-butane

The substantially same method as described in Preparation Example 69 was conducted, except that l-(2,4-dichlorophenyl)-3-methyl-(R,R)-l,2-butanediol(Prepara tion example33)was used instead of l-(2-chlorophenyl)-(S,S)-l ,2-propanediol(Preparation examplel4) to obtain the title compound (3.5g, yield 90~120%).

Ή NMR(400MHz, CDCl ₃ )5-0.053(s, 9H), 0.044(s, 9H), 1.00(d, J=6.8Hz, 6H), 1.60~1.65(m, 1H), 4.13~4.18(m, 1 H), 5.36(t, J=7.6Hz, 1H), 7.30~7.53(m, 3H)

Preparation Example 98 : Preparation of l-(2,6-dichlorophenyl)-3-methyl- (R,R)-l,2-(Bis-trimethyIsilanyloxy)-butane

The substantially same method as described in Preparation Example 69 was conducted, except that l-(2,6-dichlorophenyl)-3-methyl-(R,R)- l,2-butanediol(Preparation example45)was used instead of l-(2-chlorophenyl)-(S,S)-l ,2-propanediol(Preparation exampleH) to obtain the title compound (3.4g, yield 90-120%).

Ή NMR(400MHz, CDCl ₃ )5-0.053(s, 9H), 0.044(s, 9H), 1.00(d, J=6.8Hz, 6H), 1.60~1.65(m, 1H), 4.13~4. 18(m, 1 H), 5.36(t, J=7.6Hz, 1H), 7.17~7.35(m, 3H) Preparation Example 99 : Preparation of l-(2,4-dichlorophenyl)-(R,R)-l,2- (Bis-trimethylsilanyloxy)-hexane

The substantially same method as described in Preparation Example 69 was conducted, . except that l-(2,4-dichlorophenyl)-(R,R)-l,2-hexanediol(Preparation example36)was used instead of l-(2-chlorophenyl)-(S,S)-l,2-propanediol(Preparation examplel4) to obtain the title compound (3.6g, yield 90-120%).

Ή NMR(400MHz, CDCl ₃ )5-0.053(s, 9H), 0.044(s, 9H), 0.89~0.93(m, 3H), 1.30~1.39(m, 2H), 1.49~1.52(m, 2H), 1.56~1.62(m, 2H), 3.72~3.77(m, 1H), 4.98(t, J=4.8Hz, 1H), 7.28~7.50(m, 3H)

Preparation Example 100 : Preparation of l-(2,6-dichlorophenyl)-(R,R)-l,2- (Bis-trimethylsilanyloxy)-hexane

The substantially same method as described in Preparation Example 69 was conducted, except that l-(2,6-dichlorophenyl)-(R,R)-l,2-hexanediol(Preparation example48)was used instead of l-(2-chlorophenyl)-(S,S)-l ,2-propanediol(Preparation examplel4) to obtain the title compound (3.3g, yield 90-120%).

Ή NMR(400MHz, CDCl ₃ )6-0.053(s, 9H), 0.044(s, 9H), 0.85(t, J=6.7Hz, 3H), 1.20-1.3 l(m, 4H), 1.45-1.53(m, 2H), 4.28~4.33(m, 1H), 5.25(t, J=8.4Hz, 1H), 7.18-7.35(m, 3H)

Preparation Example 101 : Preparation of l-(2,4-dichlorophenyl)-l,2-(Bis- trimethylsilanyloxy)-propane

The substantially same method as described in Preparation Example 69 was conducted, except that l-(2,4-dichlorophenyl)-l ,2-propanediol(Preparation example28)was used instead of l -(2-chlorophenyl)-(S,S)-l ,2-propanediol(Preparation exampleH) to obtain the title compound (2.6g, yield 90-120%).

Ή NMR(400MHz, CDCl ₃ )8-0.053(s, 9H), 0.044(s, 9H), 1.22(d, J=6.4Hz, 3H), 3.90~3.95(m, 1H), 4.94(t, J=5.0Hz, 1H), 7.3 l~7.49(m, 3H)

Preparation Example 102 : Preparation of l-(2,6-dichlorophenyl)-l,2-(Bis- trimethylsiIanyloxy)-propane

The substantially same method as described in Preparation Example 69 was conducted, except that l-(2,6-dichlorophenyl)-l ,2-propanediol(Preparation example40)was used instead of l-(2-chlorophenyl)-(S,S)-l,2-propanediol(Preparation exampleH) to obtain the title compound (3. lg, yield 90-120%).

Ή NMR(400MHz, CDCl ₃ )8-0.053(s, 9H), 0.044(s, 9H), 1.10(d, J=6.4Hz, 3H), 4.47~4.54(m, 1H), 5.24(t, J=8.8Hz, 1H), 7.18~7.36(m, 3H)

Preparation Example 103 : Preparation of l-(2,3-dichlorophenyl)-l,2-(Bis- trimethylsilanyloxy)-propane

The substantially same method as described in Preparation Example 69 was conducted, except that l-(2,3-dichlorophenyl)-l ,2-propanediol(Preparation example59)was used instead of l-(2-chlorophenyl)-(S,S)-l,2-propanediol(Preparation exampleH) to obtain the title compound (2.7g, yield 90-120%).

Ή NMR(400MHz, CDCl ₃ )5-0.053(s, 9H), 0.044(s, 9H), 1.10(d, J=6.4Hz, 3H), 4.47~4.54(m, 1H), 5.24(t, J=8.8Hz, 1 H), 7.18~7.22(m, 3H)

Preparation Example 104 : Preparation of l-(2,4-dichlorophenyl)-l,2-(Bis- trimethylsilanyloxy)-butane

The substantially same method as described in Preparation Example 69 was conducted, except that l-(2,4-dichlorophenyl)-l ,2-butanediol(Preparation exam pi e31 )was used instead of l-(2-chlorophenyl)-(S,S)-l ,2-propanediol(Preparation examplel4) to obtain the title compound (2.9g, yield 90-120%).

Ή NMR(400MHz, CDCl ₃ )8-0.053(s, 9H), 0.044(s, 9H), 1.02(t, J=7.4Hz, 3H), 1.54~1.61(m, 2H), 3.65~3.68(m, 1H), 5.01 (t, J=5.0Hz, 1 H), 7.31~7.49(m, 3H)

Preparation Example 105 Preparation of l-(2,6-dichlorophenyI)-l,2-(Bis- trimethylsilanyloxy)-butane

The substantially same method as described in Preparation Example 69 was conducted, except that l-(2,6-dichlorophenyl)-l ,2-butanediol(Preparation example43)was used instead of l-(2-chlorophenyl)-(S,S)-l ,2-propariediol(Preparation examplel4) to obtain the title compound (3.1 g, yield 90-120%).

lH NMR(400MHz, CDCl ₃ )5-0.053(s, 9H), 0.044(s, 9H), 0.97(t, J=7.6Hz, 3H), 1.26~1.53(m, 2H), 4.22~4.26(m, 1H), 5.26(t, J=8.4Hz, 1H), 7.17~7.35(m, 3H)

Preparation Example 106 : Preparation of l-(2,4-dichlorophenyl)-3-methyl- l,2-(Bis-trimethylsilanyloxy)-butane

The substantially same method as described in Preparation Example 69 was conducted, except that l-(2,4-dichlorophenyl)-3-methyl-l ,2-butanediol(Preparation example34)was used instead of l -(2-chlorophenyl)-(S,S)-l,2-propanediol(Preparation example 14) to obtain the title compound (2.7g, yield 90-120%).

Ή NMR(400MHz, CDCl ₃ )5-0.053(s, 9H), 0.044(s, 9H), 1.00(d, J=6.8Hz, 6H), 1.60~l ,65(m, 1H), 4.13~4.18(m, 1H), 5.36(t, J=7.6Hz, 1H), 7.30~7.53(m, 3H) Preparation Example 107 : Preparation of l-(2,6-dichlorophenyl)-3-methyl- l,2-(Bis-trimethylsilanyloxy)-butane

The substantially same method as described in Preparation Example 69 was conducted, except that l-(2,6-dichlorophenyl)-3-methyl-l ,2-butanediol(Preparation example46)was used instead of l-(2-chlorophenyl)-(S,S)-l ,2-propanediol(Preparation examplel4) to obtain the title compound (2.6g, yield 90-120%).

Ή NMR(400MHz, CDCl ₃ )5-0.053(s, 9H), 0.044(s, 9H), 1.00(d, J=6.8Hz, 6H), 1.60~1.65(m, lH), 4.13~4.18(m, 1H), 5.36(t, J=7.6Hz, 1H), 7.17~7.35(m, 3H)

Preparation Example 108 : Preparation of l-(2,4-dichlorophenyl)-l,2-(Bis- trimethylsilanyloxy)-hexane

The substantially same method as described in Preparation Example 69 was conducted, except that l-(2,4-dichlorophenyl)- l,2-hexanediol(Preparation example37)was used instead of l-(2-chlorophenyl)-(S,S)-l,2-propanediol(Preparation examplel4) to obtain the title compound (3.7g, . yield 90-120%).

Ή NMR(400MHz, CDCl ₃ )6-0.053(s, 9H), 0.044(s, 9H), 0.89~0.93(m, 3H), 1.30~1.39(m, 2H), 1.49-1.52(m, 2H), 1.56~1.62(m, 2H), 3.72~3.77(m, 1 H), 4.98(t, J=4.8Hz, 1H), 7.28-7.50(m, 3H)

Preparation Example 109 : Preparation of l-(2,6-dichlorophenyl)-l,2-(Bis- trimethylsilanyloxy)-hexane

The substantially same method as described in Preparation Example 69 was conducted, except that l-(2,6-dichlorophenyl)- l ,2-hexanediol(Preparation example49)was used instead of l-(2-chlorophenyl)-(S,S)-l ,2-propanediol(Preparation example 14) to obtain the title compound (3.2g, yield 90-120%).

Ή NMR(400MHz, CDCl ₃ )5-0.053(s, 9H), 0.044(s, 9H), 0.85(t, J=6.7Hz, 3H), 1.20-1.3 l (m, 4H), 1.45~1.53(m, 2H), 4.28~4.33(m, 1H), 5.25(t, J=8.4Hz, 1H), 7.18~7.35(m, 3H)

Preparation Example 110 : Preparation of l-(2-fluoroophenyl)-(S,S)-l,2-(Bis- trimethylsilanyloxy)-propane

The substantially same method as described in Preparation Example 69 was conducted, except that l-(2-fluoroophenyl)-(S,S)-l ,2-propanediol(Preparation example61)was used instead of l-(2-chlorophenyl)-(S,S)-l,2-propanediol(Preparation examplel4) to obtain the title compound (2.8g, yield 90-120%).

Ή NMR(400MHz, CDCl ₃ )5-0.053(s, 9H), 0.044(s, 9H), 1.15(d, J=6.4Hz, 3H), 3.90~3.98(m, lH), 4.78(dd, J=4.4, 7.2Hz, 1H), 7.04~7.50(m, 4H)

Preparation Example 111 : Preparation of l-(2-fulorophenyl)-(R,R)-l,2-(Bis- trimethylsilanyIoxy)-propane

The substantially same method as described in Preparation Example 69 was conducted, except that l -(2-fluoroophenyl)-(R,R)-l,2-propanediol(Preparation example62)was used instead of l-(2-chlorophenyl)-(S,S)-l ,2-propanediol(Preparation examplel4) to obtain the title compound (2.5g, yield 90-120%).

Ή NMR(400MHz, CDCl ₃ )5-0.053(s, 9H), 0.044(s, 9H), 1.15(d, J=6.4Hz, 3H), 3.90~3.98(m, 1 H), 4.78(dd, J=4.4, 7.2Hz, 1H), 7.04-7.50(m, 4H)

Preparation Example 112 : Preparation of l-(2-iodophenyl)-(S,S)-l,2-(Bis- trimethylsilanyloxy)-propane

The substantially same method as described in Preparation Example 69 was conducted, except that l-(2-iodophenyl)-(S,S)-l ,2-propanediol(Preparation example66)was used instead of l-(2-chlorophenyl)-(S,S)- l,2-propanediol(Preparation example 14) to obtain the title compound (3. lg, yield 90-120%).

Ή NMR(400MHz, CDCl ₃ )5-0.053(s, 9H), 0.044(s, 9H), 1.27(d, J=6.4Hz, 3H), 3.99(t, J=6.0Hz, 1H), 4.81 (d, J=4.0Hz, 1H), 7.01~7.87(m, 4H)

Preparation Example 113 : Preparation of l-(2-iodophenyl)-(R,R)-l,2-(Bis- trimethylsilanyloxy)-propane

The substantially same method as described in Preparation Example 69 was conducted, except that l-(2-iodophenyl)-(R,R)-l,2-propanediol(Preparation example67)was used instead of l -(2-chlorophenyl)-(S,S)-l,2-propanediol(Preparation examplel4) to obtain the title compound (2.8g, yield 90-120%).

Ή NMR(400MHz, CDCl ₃ )6-0.053(s, 9H), 0.044(s, 9H), 1.26(d, J=6.4Hz, 3H), 3.98(t, J=6.2Hz, 1H), 4.88(d, J=4.4Hz, 1H), 7.00~7.87(m, 4H)

Preparation Example 114 : Preparation of l-(2-iodophenyl)-(S,S)-l,2-(Bis- trimethylsilanyloxy)-butane

The substantially same method as described in Preparation Example 69 was conducted, except that l-(2-iodophenyl)-(S,S)- l,2-butanediol(Preparation example68)was used instead of l -(2-chlorophenyl)-(S,S)-l ,2-propanediol(Preparation examplel4) to obtain the title compound (3.3g, yield 90-120%).

Ή NMR(400MHz, CDCl ₃ )5-0.053(s, 9H), 0.044(s, 9H), 1.04(t, J=7.6Hz, 3H), .71(m, 2H), 3.71 ~3.76(m, 1 H), 4.87(d, J=4.8Hz, 1 H), 7.01-7.87(m, 4H) Example 1 : Preparation of l-(2-chlorophenyl)-(S)-l-hydroxypropyl-(S)-2- carbamate(l)

To a stirred solution of crude l-(2-chlorophenyl)-(S,S)-l,2-(Bis-trimethylsilanyloxy) propane(preparation example69, 104g, 0.31mol) in toluene (670mL) was added by

Chlorosulfonyl isocynate(62.5mL, 0.71mol) at 0°C. The reaction mixture was stirred for 2hr.

The reaction mixture was quenched with ice water and then was stirred by additional cold H ₂ 0 (500mL) for 2hr. After separation of organic layer, the aqueous was adjusted pH2~3 with sat. NaHCO ₃ (400mL) and extracted with EtOAc (300mL x3). The EtOAc layer was washed with sat. NaHC0 ₃ (500mL) and H ₂ O(500mL). The organic phase was treated with Charcol for 1.5hr. The organic phase was filtered with Cellite, dreid over MgS0 ₄ . Filterion and concentration under vacuum provided the title compound of white solid(yield

85%(71.1g), ee = 99.9% MP = 83~84°C, [a] _D =+57.8(c=0.25, MeOH))

Ή NMR(400MHz, CDC1 ₃ ) 51.24(d, J=6.4, 3H), 2.91(d, J=4.8, 1H), 4.68(br s, 2H), 5.06~5.09(m, 1H), 5.18~5.21 (m, 1 H), 7.23~7.39(in, 3H), 7.55(dd, J=1.6, J=7.8, 1 H)

1 ³ C NMR(100MHz, CDC1 ₃ ) 616.4, 73.1, 75.0, 127.0, 128.4, 129.1, 129.5, 132.7, 138.0, 156.6

Example 2 : Preparation of l-(2-chlorophenyl)-(R)-l-hydroxypropyl-(R)-2- carbamate(2)

The substantially same method as described in Example 1 was conducted, except that l-(2-chlorophenyl)-(R,R)- l ,2-(Bis-trimethylsilanyloxy) propane (Preparation example70)was used instead of l-(2-chlorophenyl)-(S,S)-l ,2-(Bis-trimethylsilanyloxy) propane (Preparation example69) to obtain the title compound (5.7g, yield 60-90%).

Ή NMR(400MHz, CDC1 ₃ ) 51.24(d, J=6.4, 3H), 2.91(d, J=4.8, 1H), 4.68(br s, 2H), 5.06~5.09(m, 1 H), 5.18-5.2 l (m, l H), 7.23~7.39(m, 3H), 7.55(dd, J=1.6, J=7.8, lH) Example 3 : Preparation of l-(2-chlorophenyl)-l-hydroxypropyl-2- carbamate(3)

The substantially same method as described in Example 1 was conducted, except that l -(2-chlorophenyl)-l,2-(Bis-trimethylsilanyloxy) propane (Preparation example71)was used instead of l-(2-chlorophenyl)-(S,S)-l,2-(Bis-trimethylsilanyloxy) propane (Preparation example69) to obtain the title compound (3.8g, yield 60~90%).

Ή NMR(400MHz, CDC1 ₃ ) 61.24(d, J=6.4, 3H), 2.9 l (d, J=4.8, 1H), 4.68(br s, 2H), 5.06~5.09(m, 1H), 5.18~5.21(m, lH), 7.23~7.39(m, 3H), 7.55(dd, J=1.6, J=7.8, 1H)

Example 4 : Preparation of l-(2-chlorophenyl)-(S)-l-hydroxypropyl-(R)-2- carbamate(4)

The substantially same method as described in Example 1 was conducted, except that l-(2-chlorophenyl)-(S,R)-l ,2-(Bis-trimethylsilanyloxy) propane (Preparation example72)was used instead of l-(2-chlorophenyl)-(S,S)-l,2-(Bis-trimethylsilanyloxy) propane (Preparation example69) to obtain the title compound (2.4g, yield 60-90%).

Ή NMR(400MHz, CDC1 ₃ ) 61.24(d, J=6.4, 3H), 2.91(d, J=4.8, 1H), 4.68(br s, 2H), 5.06~5.09(m, 1 H), 5. l 8~5.21 (m, 1H), 7.23~7.39(m, 3H), 7.55(dd, J=1.6, J=7.8, 1H)

Example 5 : Preparation of l-(2-chlorophenyl)-(R)-l-hydroxypropyl-(S)-2- carbamate(5)

The substantially same method as described in Example 1 was conducted, except that l-(2-chlorophenyl)-(R,S)-l ,2-(Bis-trimethylsilanyloxy) propane (Preparation example73)was used instead of l -(2-chlorophenyl)-(S,S)- l ,2-(Bis-trimethylsilanyloxy) propane (Preparation example69) to obtain the title compound (2.3g, yield 60~90%).

Ή NMR(400MHz, CDC1 ₃ ) 61.24(d, J=6.4, 3H), 2.91(d, J=4.8, 1H), 4.68(br s, 2Ή), 5.06~5.09(m, IH), 5.18~5.21 (m, 1 H), 7.23~7.39(m, 3H), 7.55(dd, J=1.6, J=7.8, 1H)

Example 6 : Preparation of l-(2-chlorophenyl)-(S)-l-hydroxybutyl-(S)-2- carbamate(6)

The substantially same method as described in Example 1 was conducted, except that l-(2- chlorophenyl)-(S,S)-l ,2-(Bis-trimethylsilanyloxy)butane (Preparation example74)was used instead of l-(2-chlorophenyl)-(S,S)- l ,2-(Bis-trimethylsilanyloxy) propane (Preparation example69) to obtain the title compound (2.6g, yield 60-90%).

Ή NMR(400MHz, CDC1 ₃ ) 60.96(t, J = 7.4 Hz, 3H), 1.57~1.73(m, 2H), 3.01(d, J = 5.6Hz, IH), 4.74(br s, 2H), 4.95(dt, J= 7.2, 8.8Hz, IH), 5.23(t, J = 5.6Hz, IH), 7.22~7.54(m, 4H)

Example 7: Synthesis of l-(2-chlorophenyl)-(R)-l-hydroxybtyl-(R)-2- carbamate(7)

The substantially same method as described in Example 1 was conducted, except that l -(2-chlorophenyl)-(R,R)-l ,2-(Bis-trimethylsilanyloxy)butane (Preparation Example 75) was used instead of l-(2-chlorophenyl)-(S,S)-l ,2-(Bis-trimethylsilanyloxy) propane (Preparation example69) to obtain the title compound (2.5g, yield 60~90%).

Ή NMR(400MHz, CDC1 ₃ ) δ 0.94(t, J=7.4Hz, 3H), 1.53~1.73(m, 2H), 2.92(s, IH), 4.78(br s, 2H), 4.91~4.96(m, IH), 5.22(d, J=5.5Hz, IH), 7.20~7.54(m, 4H)

Example 8: Synthesis of l-(2-chlorophenyl)-l-hydroxybutyI-2-carbamate(8)

The substantially same method as described in Example 1 was conducted, except that

1- (2-chlorophenyl)-l,2-(Bis-trimethylsilanyloxy)butane (Preparation Example 76) was used instead of l -(2-chlorophenyl)-(S,S)-l ,2-(Bis-trimethylsilanyloxy) propane (Preparation example69) to obtain the title compound (1.9g, yield 60-90%).

Ή NMR(400MHz, CDCI ₃ ) δ 0.97(t, J=7Hz, 3H), 1.58~1.74(m, 2H), 2.94(d, J=6Hz, 1H), 4.69(br s, 2H), 4.94~4.99(m, 1H), 5.24(t, J=6Hz, 1H), 7.23~7.56(m, 4H)

Example 9: Synthesis of l-(2-chlorophenyl)-(S)-l-hydroxy-3-methyl-butyl-(S)-

2- carbamate(9)

The substantially same method as described in Example 1 was conducted, except that 1 -(2-chlorophenyl)-3-methyl-(S,S)-l ,2-(Bis-trimethylsilanyloxy)butane (Preparation Example 77) was used instead of l -(2-chlorophenyl)-(S,S)-l ,2-(Bis-trimethylsilanyloxy) propane (Preparation example69) to obtain the title compound (1.7g, yield 60~90%).

Ή NMR(400MHz, CDC1 ₃ ) 61.01(d, J = 6.4Hz, 3H), 1.09(d, J = 6.8Hz, 3H), 2.06(m, 1H), 2.75(d, J= 6.8Hz, 1H), 4.58(br s, 2H), 4.85~4.88(m, 1H), 5.34~5.37(m, 1H),

7.22~7.33(m, 2H), 7.35~7.37(m, 1 H), 7.5 l~7.53(m, 1 H)

Example 10: Synthesis of l-(2-chlorophenyl)-(R)-l-hydroxy-3-methyl-butyl- (R)-2-carbamate(10)

The substantially same method as described in Example 1 was conducted, except that l-(2-chlorophenyl)-3-methyl-(R,R)-l ,2-(Bis-trimethylsilanyloxy)butane (Preparation

Example 78) was used instead of l -(2-chlorophenyl)-(S,S)- l ,2-(Bis-trimethylsilanyloxy) propane (Preparation example69) to obtain the title compound (1.6g, yield 60-90%). Ή NMR(400MHz, CDC1 ₃ ) 61.01 (d, J= 6.8Hz, 3H), 1.09(d, J= 6.8Hz, 3H), 2.06(m, 1H), 2.73(d, J= 6.8Hz, 1H), 4.57(br s, 2H), 4.85~4.88(m, 1H), 5.34~5.37(m, 1 H),

7.24~7.30(m, 2H), 7.35~7.37(m, 1 H), 7.51~7.53(m, l H)

Example 11: Synthesis of l-(2-chlorophenyl)-l-hydroxy-3-methyl-butyl-2- carbamate(ll)

The substantially same method as described in Example 1 was conducted, except that l-(2-chloroph en yl)-3 -methyl- l,2-(Bis-trimethylsilanyloxy)butane (Preparation Example 79) was used instead of l-(2-chlorophenyl)-(S,S)-l,2-(Bis-trimethylsilanyloxy) propane (Preparation example69) to obtain the title compound (1.7g, yield 60-90%).

Ή NMR(400MHz, CDCI3) 61.00(d, J=6.4Hz, 3H), 1.09(d, J=6.4Hz, 3H), 2.08(m, 1H), 2.76(d, J=6.0Hz, 1H), 4.59(br s, 2H), 4.87(dd, J=7.2Hz, 4.4Hz, 1H), 5.36(t, J=4.6, 1H), 7.23~7.54(m, 4H)

Example 12: Synthesis of l-(2-chlorophenyl)-(S)-l-hydroxyhexyl-(S)-2- carbam

The substantially same method as described in Example 1 was conducted, except that l-(2-chlorophenyl)-(S,S)-l ,2-(Bis-trimethylsilanyloxy)hexane (Preparation Example 80) was used instead of l-(2-chlorophenyl)-(S,S)- l,2-(Bis-trimethylsilanyloxy) propane (Preparation example69) to obtain the title compound (2.3g, yield 60-90%).

'H NMR(400MHZ, CDC1 ₃ ) 50.88(t, J= 7Hz, 3H), 1.33~1.42(m, 4H), 1.53-1.7 l (m, 2H), 2.89(d, J= 5.6Hz, 1 H) 4.64(br s, 2H), 5.04(dt, J= 5.0, 9.0Hz, 1H), 5.20(t, J= 5.6Hz, 1H), 7.23~7.55(m, 4H)

Example 13: Synthesis of l-(2-chlorophenyl)-(R)-l-hydroxyhexyl-(R)-2- carbamate(13)

The substantially same method as described in Example 1 was conducted, except that l -(2-chlorophenyl)-(R,R)-l ,2-(Bis-trimethylsilanyloxy)hexane (Preparation Example 81 ) was used instead of l -(2-chlorophenyl)-(S,S)- l,2-(Bis-trimethylsilanyloxy) propane (Preparation example69) to obtain the title compound (2.2g, yield 60-90%).

Ή NMR(400MHz, CDC1 ₃ ) δ 0.89(dd, J=5Hz, 3H), 1.28~l .43(m, 4H), 1.52~1.58(m, 1H), 1.65~1.72(m, 1H), 2.90(d, J=6Hz, l H), 4.64(br s, 2H), 5.01~5.06(m, 1H), 5.22(t, J=6Hz, 1H), 7.22~7.56(m, 4H)

Example 14: Synthesis of l-(2-chlorophenyl)-l-hydroxyhexyI-2-carbamate(14)

The substantially same method as described in Example 1 was conducted, except that l-(2-chlorophenyl)-l,2-(Bis-trimethylsilanyloxy)hexane (Preparation Example 82) was used instead of l-(2-chlorophenyl)-(S,S)-l,2-(Bis-trimethylsilanyloxy) propane (Preparation example69) to obtain the title compound (2.1 g, yield 60-90%).

Ή NMR(400MHz, CDC1 ₃ ) δ 0.88(dd, J=5Hz, 3H), 1.31~1.43(m, 4H), 1.63~1.70(m, 1H), 1.52~1.60(m, 1H), 3.06(d, J=6Hz, 1H), 4.75(br s, 2H), 5.00~5.05(m,TH), 5.21 (t, J=6Hz, 1H), 7.22~7.55(m, 4H)

Example 15: Synthesis of l-(2-chlorophenyl)-(S)-l-hydroxypropyl-(S)-2-N- methylcarbamate(15)

l-(2-chlorophenyl)-(S,S)-l,2-propanediol(2.4g) obtained in Preparation Example 14, tetrahydrofuran (THF, 12ml), and carbonyldiimidazole (CDI, 3.12g) were put into a flask and stirred at the room temperature. After approximately 3 hours, methylamine solution(CH ₃ NH ₂ , 4ml(33% in EtOH)) was added thereto. When the reaction was completed, the obtained product was washed with 1M HCl solution and ethylacetate (EA). The separated organic layer was dehydrated with anhydrous magnesium sulfate (MgS0 ₄ ), filtrated, and concented under reduced pressure. The concentrated residue was purified by a silica gel column chromatography, to obtain the title compound (1.6g, yield 51%).

Ή NMR(400MHz, CDC1 ₃ ) 51.03~1.25(m, 3H), 2.76(s, 3H), 3.34(s, 1 H), 4.80(br s 1 H), 5.04(t, J=12.5Hz, 1H), 5.14(s, 1H), 7.20~7.53(m, 4H)

Example 16: Synthesis of l-(2-chlorophenyl)-(S)-l-hydroxypropyl-(S)-2-N- propylcarbamate 16)

The substantially same method as described in Example 15 was conducted, except that propylamine was used instead of methylamine solution(CH ₃ NH ₂ in EtOH), to obtain the title compound (0.79g, yield 25%).

Ή NMR(400MHz, CDC1 ₃ ) 50.90(t, J=6.8Hz, 3H), 1.20(d, J=5.96Hz, 3H), 1.49(dd, J=l4.2Hz, 2H), 3.11 (d, J=6.28Hz, 2H), 3.34(s, 1H), 4.84(br s, lH), 5.05(t, J=5.88Hz, 1H), 5.14(s, 1 H), 7.22~7.53(m, 4H)

Example 17: Synthesis of l-(2-chlorophenyl)-(S)-l-hydroxypropyI-(R)-2-N- isoprop lcarbamate(17)

The substantially same method as described in Example 15 was conducted, except that isopropylamine was used instead of methylamine solution(CH ₃ NH? in EtOH), to obtain the title compound (1.5g, yield 41%).

Ή NMR(400MHz, CDC1 ₃ ) 51.14(dd, J=6.5Hz, 6H), 1.19(d, J=6.4Hz, 3H), 3.21 (s, 1 H), 3.73~3.82(m, 1 H), 4.59(br s, 1H), 5.01~5.07(m, 1 H), 5.14(t, J=5.8Hz, 1 H), 7.20~7.53(m, 4H) Example 18: Synthesis of l-(2-chlorophenyl)-(S)-l-hydroxypropyI-(R)-2-N- cyclopro lcarbamate(18)

The substantially same method as described in Example 15 was conducted, except that cyclopropylamine was used instead of methylamine solution(CH ₃ NH ₂ in EtOH), to obtain the title compound (2.2g, yield 43%).

Ή NMR(400MHz, CDC1 ₃ ) 80.50~0.56(m, 2H), 0.74(d, J=7.21Hz, 2H), 1.25(s, 3H), 2.56~2.61(m, 1H), 3.72(s, 1H), 4.98(br s, 1H), 5.05-5. l l(m, 1H), 7.16(s, 1H), 7.23~7.54(m, 4H)

Example 19: Synthesis of l-(2-chlorophenyl)-(S)-l-hydroxypropyl-(R)-2-N- cyclohex l carbamate(19)

The substantially same method as described in Example 15 was conducted, except that cyclohexylamine was used instead of methylamine solution(CH ₃ NH ₂ in EtOH), to obtain the title compound (l . lg, yield 26%).

Ή NMR(400MHz, CDC1 ₃ ) 61.06~1.40(m, 7H), 1.56~1.61(m, 2H), 1.69~1.71(m, 2H), 1.87~l .94(m, 2H), 3.19(d, J=4.32Hz, 1H), 3.45(s, 1H), 4.64(br s 1 H), 5.02~5.07(m, 1 H), 5.14(t, J=6.08Hz, 1H) 7.20~7.53(m, 4H)

Example 20: Synthesis of l-(2-chlorophenyl)-(S)-l-hydroxypropyl-(S)-2-N- benzyl carbamate(20)

The substantially same method as described in Example 15 was conducted, except that benzylamine was used instead of methylamine solution(CH ₃ NH2 in EtOH), to obtain the title compound (1.2g, yield 18%).

Ή NMR(400MHz, CDC1 ₃ ) δ 1.27(d, J=10Hz, 3H), 3.12(d, J=5Hz, 1H), 4.37(d, J=6Hz, 2H), 5.12~5.19(m, 3H), 7.15~7.56(m, 9H)

Example 21: Synthesis of l-(2-chlorophenyl)-(S)-l-hydroxypropyl-(S)-2- N- bicyclo[2 2,l]heptanescarbamate(21)

The substantially same method as described in Example 15 was conducted, except that 2-aminonorbornane was used instead of methylamine solution(CH ₃ NH ₂ in EtOH), to obtain the title compound (1.7g, yield 32%).

Ή NMR(400MHz, CDC1 ₃ ) 61.08~1.35(m, 9H), 1.65(br s, 1 H), 1.75~1.71 (m, 1H), 2.14~2.24(m, 1H), 2.27~2.30(m, 1H), 3.23~3.29(m, 1H), 3.47~3.52(m, 1H), 4.67(br s, 1H), 5.01~5.09(m, 1H), 5.12~5.18(m, 1H), 7.22~7.55(m, 4H)

Example 22: Synthesis of l-(2-chlorophenyl)-(R)-l-hydroxypropyl-(R)-2- N- methylcarbamate(22)

The substantially same method as described in Example 15 was conducted, except that l-(2-chlorophenyl)-(R,R)-l ,2-propanediol(Preparation example 15) was used instead of l-(2-chlorophenyl)-(S,S)- l,2-propanediol(Preparation example 14), to obtain the title compound (3.36g, yield 60%).

Ή NMR(400MHz, CDC1 ₃ ) δ 1.20(d, J=6.8Hz, 3H), 2.80(d, J=4.8Hz, 3H), 3.20(d, J=4.4Hz, 1H), 4.75(br s, 1 H), 5.03~5.09(m, 1H), 5.14~5.17(m, 1 H), 7.22~7.55(m, 4H)

Example 23: Synthesis of l-(2-chlorophenyl)-(R)-l-hydroxypropyl-(R)-2- N- propylcarbamate(23)

The substantially same method as described in Example 22 was conducted, except that propylamine was used instead of methylamine solution(CH ₃ NH ₂ in EtOH), to obtain the title compound (3.1 g, yield 53%).

Ή NMR(400MHz, CDC1 ₃ ) 50.92(t, J=7.6Hz, 3H), 1.21 (d, J=6.4Hz, 3H), 1.51(m, 2H), 3.09-3.14(m, 2H), 3.28(d, J=4.4Hz, 1H), 4.82(br s, 1H), 5.03~5.09(m, 1 H), 5.14-5.17(m, 1H), 7.22~7.55(m. 4H)

Example 24: Synthesis of l-(2-chlorophenyl)-(R)-l-hydroxypropyl-(R)-2- N- isopropyIcarbamate(24)

The substantially same method as described in Example 22 was conducted, except that isopropylamine was used instead of methylamine solution(CH ₃ NH? in EtOH), to obtain the title compound (0.16g, yield 27%).

Ή NMR(400MHz, CDC1 ₃ ) 50.88~1.16(m, 6H), 1.19~1.26(m, 3H), 3.34(s, 1H), 3.71~3.78(m, 1H), 4.62(br s, 1 H), 5.03(t, J=5.8Hz, 1H), 5.13(d, J=4.9Hz, 1H), 7.20-7.53(m, 4H)

Example 25: Synthesis of l-(2-ch!orophenyl)-(R)-l-hydroxypropyl-(R)-2- N- cyclopro lcarbamate(25)

The substantially same method as described in Example 22 was conducted, except that cyclopropylamine was used instead of methylamine solution(CH ₃ NH ₂ in EtOH), to obtain the title compound (3.7g, yield 60%).

Ή NMR(400MHz, CDC1 ₃ ) 60.49~0.54(m, 2H), 0.74(d; ^" J=7.2Hz, 2H), 1.22(s, 3H), 2.55~2.60(m, 1 H), 3.16(s, 1H), 5.00(s, 1 H), 5.04-5.1 l (m, 1H), 5.16(s, 1 H), 7.23~7.54(m, 4H)

Example 26: Synthesis of l-(2-chlorophenyl)-(R)-l-hydroxypropyl-(R)-2- N- cyclohexyl carbamate(26)

The substantially same method as described in Example 22 was conducted, except that cyclohexylamine was used instead of methylamine solution(CH ₃ NH ₂ in EtOH), to obtain the title compound (1.9g, yield 28%).

Ή NMR(400MHz, CDC1 ₃ ) 51.05~1.38(m, 8H), 1.58~1.70(m, 3H), 1.85~1.95(m, 2H), 3.39-~3.47(m, 1H), 3.56(s, 1H), 4.79(br s, 1H), 5.01~5.07(m, 1H), 5.14(t, J=5.2Hz, 1H), 7.20~7.54(m, 4H)

Example 27: Synthesis of l-(2-chlorophenyl)-(R)-l-hydroxypropyI-(R)-2- N- benzylcarbamate(27)

The substantially same method as described in Example 22 was conducted, except that benzylamine was used instead of methylamine solution(CH3NH ₂ in EtOH), to obtain the title compound (0.52g, yield 19%).

Ή N R(400MHz, CDC1 ₃ ) 61.25(d, J=6Hz, 3H), 1.64(s, 1H), 3.13(d, J=4.4Hz, 1H), 4.37(d, J=5.6Hz, 2H), 5.12~5.19(m, 2H), 7.23~7.55(m, 9H)

Example 28: Synthesis of l-(2-chIorophenyI)-(R)-l-hydroxypropyl-(R)-2- N- bicyclo[2 2,l]heptanecarbamate(28)

The substantially same method as described in Example 22 was conducted, except that 2-aminonorbornane was used instead of methylamine solution(CH ₃ NH2 in EtOH), to obtain the title compound (1.7g, yield 20-50%).

Ή NMR(400MHz, CDC1 ₃ ) 51.08~1.35(m, 9H), 1.65(br s, IH), 1.75~1.71(m, IH), 2.14~2.24(m, I H), 2.27~2.30(m, IH), 3.23~3.29(m, IH), 3.47~3.52(m, IH), 4.67(br s, I H), 5.01~5,09(m, IH), 5.12~5.18(m, IH), 7.22~7.55(m, 4H)

Example 29: Synthesis of l-(2-chlorophenyl)-l-hydroxypropyl-2- N- methylcarbamate 29)

The substantially same method as described in Example 15 was conducted, except that l -(2-chlorophenyl)-l ,2-propanediol(Preparation example 16) was used instead of l -(2- chlorophenyl)-(S,S)-l,2-propanediol(Preparation example 14), to obtain the title compound (2.6g, yield 45%).

Ή NMR(400MHz, CDC1 ₃ ) δ 1.21 (d, J=6Hz, 3H), 2.81 (d, J=5Hz, 3H), 3.14(d, J=4Hz, lH), 4.72(br s, IH), 5.07(dd, J=6Hz, I H), 5.16(t, J=6Hz, IH), 7.22~7.56(m, 4H)

Example 30: Synthesis of l-(2-chlorophenyl)-l-hydroxypropyl-2- N- propylcarbamate 30)

The substantially same, method as described in Example 29 was conducted, except that propylamine was used instead of methylamine solution(CH ₃ NH ₂ in EtOH), to obtain the title compound (l .Og, yield 17%).

Ή NMR(400MHz, CDC1 ₃ ) δ 0.92(t, J=7Hz, 3Η), 1.21 (d, J=6Hz, 3Η), 1.53(dd, J=7Hz, 2H), 3.13(dd, J=7Hz, 2H), 3.28(d, IH), 4.82(S, IH), 5.06(dd, J=7Hz, IH), 5.16(t, J=5Hz, I H), 7.21~7.56(m, 4H)

Example 31: Synthesis of l-(2-chlorophenyl)-l-hydroxypropyl-2- N- isoprop lcarbamate(31)

The substantially same method as described in Example 29 was conducted, except that isopropylamine was used instead of methylamine solution(CH ₃ NH2 in EtOH), to obtain the title compound (0.54g, yield 16%).

Ή NMR(400MHz, CDC1 ₃ ) δ 1.16(dd, J=6Hz, 6H), 1.21(d, J=6Hz, 3H), 3.23(d, J=6Hz, 1H), 3.75-3.84(m, IH), 4.61(br s, 1H), 5.06(t, J=6Hz, 1H), 5.16(t, J=6Hz, 1H), 7.22~7.56(m, 4H)

Example 32: Synthesis of l-(2-chlorophenyl)-l-hydroxypropyl-2- N- cyclopropylcarbamate(32)

The substantially same method as described in Example 29 was conducted, except that cyclopropylamine was used instead of methylamine solution(CH ₃ NH ₂ in EtOH), to obtain the title compound (1.0g, yield 17%).

Ή NMR(400MHz, CDC1 ₃ ) δ 0.50( J=6Hz, 2H), 0.77(t, J=3Hz, 2H), 1.12(d, J=7Hz, 3H), 2.53~2.59(m, 1H), 3.22(d, J=4Hz, 1H), 5.08(dd, J=6Hz, IH), 5.15(S, IH), 7.22~7.55(m, 4H)

Example 33: Synthesis of l-(2-chlorophenyl)-l-hydroxypropyl-2- N- cyclohex lcarbamate(33)

The substantially same method as described in Example 29 was conducted, except that cyclohexylamine was used instead of methylamine solution(CH ₃ NH2 in EtOH), to obtain the title compound (2.2g, yield 33%).

Ή NMR(400MHz, CDC1 ₃ ) δ 1.07-1.17(m, 3H), 1.21(d, J=6Hz, 3H), 1.29~1.42(m, 3H), 1.72(dd, J=6Hz, 2H), 1.92(dd, J=6Hz, 2H), 3.26(d, J=4Hz, IH), 3.46(t, J=4Hz, IH), 4.68(d, J=6Hz, IH), 5.07(dd, J=6Hz, IH), 5.16(t, J=6Hz, IH), 7.22~7.55(m, 4H)

Example 34: Synthesis of l-(2-chlorophenyl)-l-hydroxypropyl-2- N- benzylcarbamate(34)

The substantially same method as described in Example 29 was conducted, except that benzylamine was used instead of methylamine solution(CH ₃ NH ₂ in EtOH), to obtain the title compound (1.3g, yield 19%).

Ή NMR(400MHz, CDC1 ₃ ) δ 1.25(d, J=6Hz, 3H), 3.16(d, J=4Hz, I H), 4.36(d, J=6Hz, 2H), 5.14(dd, J=6Hz, 3H), 7.23~7.56(m, 9H), yield: 19%(1.3g)

Example 35: Synthesis of l-(2-chlorophenyI)-l-hydroxypropyl-2- N- bicyclo[2,2,l]heptanecarbamate(35)

The substantially same method as described in Example 29 was conducted, except that 2-aminonorbornane was used instead of methylamine solution(CH ₃ NH ₂ in EtOH), to obtain the title compound (1.7g, yield 20~50%).

Ή NMR(400MHz, CDC1 ₃ ) 61.08~1.35(m, 9H), 1.65(br s, I H), 1.75~1.71(m, IH), 2. l4~2.24(m, I H), 2.27~2.30(m, IH), 3.23~3.29(m, I H), 3.47~3.52(m, I H), 4.67(br s, I H), 5.01~5.09(m, IH), 5.12~5.18(m, I H), 7.22~7.55(m, 4H)

Example 36: Synthesis of l-(2,4-dichlorophenyl)-(S)-l-hydroxypropyl-(S)-2- carbamate(36)

The substantially same method as described in Example 1 was conducted, except that l-(2,4-dichlorophenyl)-(S,S)-l ,2-(Bis-trimethylsilanyloxy)propane (Preparation Example 83) was used instead of l -(2-chlorophenyl)-(S,S)- l ,2-(Bis-trimethylsilanyloxy) propane

(Preparation example69) to obtain the title compound (1.8g, yield 60-90%).

Ή NMR(400MHz, CDCI3) 6 l .22(d, J = 6.4Hz, 3H), 4.16(br t, 1H) 4.96(br t, 3H), 5.07(t, J = 4.8Hz, 1H), 7.23~7.52(m, 3H)

Example 37: Synthesis of l-(2,6-dichlorophenyl)-(S)-l-hydroxypropyl-(S)-2- carbamate(37)

The substantially same method as described in Example 1 was conducted, except that l-(2,6-dichlorophenyl)-(S,S)-l ,2-(Bis-trimethylsilanyloxy)propane (Preparation Example 84) was used instead of l-(2-chlorophenyl)-(S,S)-l,2-(Bis-trimethylsilanyloxy) propane

(Preparation example69) to obtain the title compound (2.6g, yield 60-90%)

Example 38 : Synthesis of l-(2,3-dichlorophenyl)-(S)-l-hydroxypropyl-(S)-2- carbamate(38)

The substantially same method as described in Example 1 was conducted, except that l-(2,3-dichlorophenyl)-(S,S)-l,2-(Bis-trimethylsilanyloxy)pr opane (Preparation Example 85) was used instead of l-(2-chlorophenyl)-(S,S)-l,2-(Bis-trimethylsilanyloxy) propane

(Preparation example69) to obtain the title compound (1.4g, yield 60-90%)

' H NMR(400MHZ, CDCI3) 61.15(d, J= 6.4Hz, 3H), 3.66(d, J = 9.2Hz, 1 H), 4.73(br s, 2H), 5.43(t, J= 9.0Hz, 1H), 5.62~5.69(m, 1H), 7.18~7.22(m, 3H),

Example 39: Synthesis of l-(2,4-dichlorophenyl)-(S)-l-hydroxybutyl-(S)-2- carbamate(39)

The substantially same method as described in Example 1 was conducted, except that l-(2,4-dichlorophenyl)-(S,S)- l ,2-(Bis-trimethylsilanyloxy)butane (Preparation Example 86) was used instead of 1 -(2-chlorophenyl)-(S,S)- 1 ,2-(Bis-trimethylsilanyloxy) propane

(Preparation example69) to obtain the title compound (2.3g, yield 60-90%).

Ή NMR(400MHz, CDC1 ₃ ) 60.96(t, J= 7.4Hz, 3H), 1.58~1.74(m, 2H), 2.98(d, J = 5.6Hz, 1H) 4.68(br s, 2H), 5.59(dt, J= 5.2, 8.8Hz, 1H), 5.19(t, J = 5.4Hz, 1H), 7.30~7.50(m, 3H)

Example 40: Synthesis of l-(2,6-dichlorophenyl)-(S)-l-hydroxybutyl-(S)-2- carbamate(40)

The substantially same method as described in Example 1 was conducted, except that l-(2,6-dichlorophenyl)-(S,S)- l ,2-(Bis-trimethylsilanyloxy)butane (Preparation Example 87) was used instead of l-(2-chlorophenyl)-(S,S)-l ,2-(Bis-trimethylsilanyloxy) propane

(Preparation example69) to obtain the title compound ( 1.7g, yield 60-90%).

Ή NMR(400MHz, CDC1 ₃ ) 60.92(t, J = 7.4Hz, 3H), 1.30~1.38(m, 1 H), 1.57-1.64(m, 1H), 3.74(d, J = 9.2Hz, 1H), 4.80(br s, 2H), 5.40~5.50(m, 2H), 7.17~7.34(m, 3H)

Example 41: Synthesis of l-(2,4-dichlorophenyl)-(S)-l-hydroxy-3-methyl- butyl-(S -2-carbamate( 1)

The substantially same method as described in Example 1 was conducted, except that l-(2,4-dichlorophenyl)-3-methyl-(S,S)-l,2-(Bis-trimethylsila nyloxy)butane (Preparation Example 88.) was used instead of l-(2-chlorophenyl)-(S,S)- l ,2-(Bis-trimethylsilanyloxy) propane (Preparation example69) to obtain the title compound (1.9g, yield 60-90%).

Ή NMR(400MHz, CDC1 ₃ ) 6 l .00(t, J= 7.2Hz, 6H), 1.73-1.79(m, 1 H), 3.67~3.69(m, 1H), 4.85(br s, 2H), 5.40~5.43(m, 1H), 5.49~5.54(m, 1H), 7.30~7.50(m, 3H)

Example 42: Synthesis of l-(2,6-dichlorophenyl)-(S)-l-hydroxy-3-methyl- butyl-(S)-2-carbamate(42)

The substantially same method as described in Example I was conducted, except that l -(2,6-dichlorophenyl)-3-methyl-(S,S)- l,2-(Bis-trimethylsilanyloxy)butane (Preparation Example 89) was used instead of l-(2-chlorophenyl)-(S,S)-l,2-(Bis-trimethylsilanyloxy) propane (Preparation example69) to obtain the title compound (2.4g, yield 60-90%).

Ή NMR(400MHz, CDC1 ₃ ) 6 l .00(t, J = 7.2Hz, 6H), 1.73~1.79(m, 1H), 3.67~3.69(m, 1H), 4.85(br s, 2H), 5.40~5.43(m, 1H), 5.49~5.54(m, 1H), 7.16~7.33(m, 3H)

Example 43: Synthesis of l-(2,4-dichlorophenyl)-(S)-l-hydroxyhexyl-(S)-2- carbamate(43)

The substantially same method as described in Example 1 was conducted, except that l-(2,4-dichlorophenyl)-(S,S)-l ,2-(Bis-trimethylsilanyloxy)hexane (Preparation Example 90) was used instead of l -(2-chlorophenyl)-(S,S)-l ,2-(Bis-trimethylsilanyloxy) propane

(Preparation example69) to obtain the title compound (2.2g, yield 60-90%).

Ή NMR(400MHz, CDC1 ₃ ) 60.89(t, J= 3.6Hz, 3H), 1.28~1.42(m, 4H), 1.52~1.59(m, 1 H), 1.64-1.71(m, 1H), 2.98(d, J= 5.6Hz, 1 H), 4.67(br s, 2H), 4.96~5.00(m, 1 H), 5.17(t, J = 5.6Hz, 1 H), 7.30~7.49(m 3H)

Example 44: Synthesis of l-(2,6-dichlorophenyl)-(S)-l-hydroxyhexyl-(S)-2- carbamate(44)

The substantially same method as described in Example 1 was conducted, except that l-(2,6-dichlorophenyl)-(S,S)-l,2-(Bis-trimethylsilanyloxy)he xane (Preparation Example 91) was used instead of l -(2-chlorophenyl)-(S,S)-l ,2-(Bis-trimethylsilanyloxy) propane

(Preparation example69) to obtain the title compound (2.1 , yield 60~90%)

Ή NMR(400MHz, CDC1 ₃ ) 60.84(t, J = 7.0Hz, 3H), 1.20~1.35(m, 4H), 1.36-1.41 (m, lH), 1.59~1.63(m, l H), 3.71(d, J= 10.0Hz, 1H), 4.74(br s, 2H), 5.40~5.44(m, 1H),

5.52~5.57(m, 1 H), 7.17~7.35(m, 3H)

Example 45: Synthesis of l-(2,4-dichlorophenyI)-(R)-l-hydroxypropyl-(R)-2- carbamate(45)

The substantially same method as described in Example 1 was conducted, except that l-(2,4-dichlorophenyl)-(R,R)-l,2-(Bis-trimethylsilanyloxy)pr opane (Preparation Example 92) was used instead of l-(2-chlorophenyl)-(S,S)-l,2-(Bis-trimethylsilanyloxy) propane

(Preparation example69) to obtain the title compound (1.2g, yield 60~90%),

Ή NMR(400MHz, CDCI ₃ ) 61.22(d, J- 6.4 Hz, 3H), 4.16(br t, 1 H) 4.96(br t, 3H), 5.07(t, J= 4.8Hz, l H), 7.23~7.52(m, 3H)

Example 46: Synthesis of l-(2,6-dichlorophenyl)-(R)-l-hydroxypropyl-(R)-2- carbamate(46)

The substantially same method as described in Example 1 was conducted, except that 1 -(2,6-dichlorophenyl)-(R,R)- 1 ,2-(Bis-trimethylsilanyloxy)propane (Preparation Example 93) was used instead of l -(2-chlorophenyl)-(S,S)-l,2-(Bis-trimethylsilanyloxy) propane

(Preparation example69) to obtain the title compound (1.7g, yield 60-90%),

Ή NMR(400MHz, CDC1 ₃ ) 61.15(d, J= 6.4Hz, 3H), 3.66(d, J = 9.2 Hz, 1 H), 4.73(br s, 2H), 5.43(t, J= 9.0Hz, lH), 5.62~5.69(m, 1 H), 7. 8~7.22(m, 3H),

Example 47: Synthesis of l-(2,3-dichlorophenyl)-(R)-l-hydroxypropyl-(R)-2- carbamate(47)

The substantially same method as described in Example 1 was conducted, except that U(2,3-dichlorophenyl)-(R,R)- l,2-(Bis-trimethylsilanyloxy)propane (Preparation Example 94) was used instead of l -(2-chlorophenyl)-(S,S)-l,2-(Bis-trimethylsilanyloxy) propane (Preparation example69) to obtain the title compound (2.0g, yield 60~90%)

Ή NMR(400MHz, CDC1 ₃ ) 51.15(d, J = 6.4Hz, 3H), 3.66(d, J = 9.2Hz, 1H), 4.73(br s, 2H), 5.43(t, J = 9.0Hz, 1H), 5.62~5.69(m, 1H), 7.18~7.22(m, 3H),

Example 48: Synthesis of l-(2,4-dichlorophenyl)-(R)-l-hydroxybutyl-(R)-2- carbamate(48)

The substantially same method as described in Example 1 was conducted, except that l-(2,4-dichlorophenyl)-(R,R)-l ,2-(Bis-trimethylsilanyloxy)butane (Preparation Example 95) was used instead of l -(2-chlorophenyl)-(S,S)-l ,2-(Bis-trimethylsilanyloxy) propane

(Preparation example69) to obtain the title compound (2.3g, yield 60-90%).

Ή NMR(400MHz, CDC1 ₃ ) 80.96(t, J= 7.4Hz, 3H), 1.58~1.74(m, 2H), 2.98(d, J = 5.6Hz, 1H) 4.68(br s, 2H), 5.59(dt, J= 5.2, 8.8Hz, 1 H), 5.19(t, J= 5.4Hz, 1H), 7.30~7.50(m, 3H)

Example 49: Synthesis of l-(2,6-dichlorophenyl)-(R)-l-hydroxybutyl-(R)-2- carbamate(49) W

The substantially same method as described in Example 1 was conducted, except that l-(2,6-dichlorophenyl)-(R,R)- l,2-(Bis-trimethylsilanyloxy)butane (Preparation Example 96) was used instead of l-(2-chlorophenyl)-(S,S)-l ,2-(Bis-trimethylsilanyloxy) propane

(Preparation example69) to obtain the title compound (2.5g, yield 60~90%).

Ή NMR(400MHz, CDC1 ₃ ) 60.92(t, J = 7.4Hz, 3H), 1.30~1.38(m, lH), 1.57~1.64(m, l H), 3.74(d, J= 9.2Hz, lH), 4.80(br s, 2H), 5.40~5.50(m, 2H), 7.17~7.34(m, 3H)

Example 50: Synthesis of l-(2,4-dichlorophenyl)-(R)-l-hydroxy-3-methyI- butyl-(R)-2-carbamate(50)

The substantially same method as described in Example 1 was conducted, except that l-(2,4-dichlorophenyl)-3-methyl-(R,R)-l,2-(Bis-trimethylsila nyloxy)butane (Preparation Example 97) was used instead of l-(2-chlorophenyl)-(S,S)-l ,2-(Bis-trimethylsilanyloxy) propane (Preparation example69) to obtain the title compound (2.8g, yield 60-90%).

' H MR(400MHZ, CDC1 ₃ ) 81.00(t, J = 7.2Hz, 6H), 1.73~1.79(m, 1H), 3.67~3.69(m, 1H), 4.85(br s, 2H), 5.40~5.43(m, 1H), 5.49~5.54(m, 1H), 7.30-7.50(m, 3H)

Example 51: Synthesis of l-(2,6-dichlorophenyl)-(R)-l-hydroxy-3-methyl- butyl-(R)-2-carbamate(51)

The substantially same method as described in Example 1 was conducted, except that l-(2,6-dichlorophenyl)-3-methyl-(R,R)-l ,2-(Bis-trimethylsilanyloxy)butane (Preparation Example 98) was used instead of l-(2-chlorophenyl)-(S,S)-l ,2-(Bis-trimethylsilanyloxy) propane (Preparation example69) to obtain the title compound (2.6g, yield 60~90%). Ή NMR(400MHz, CDCI3) δ 1.00(t, J = 7.2Hz, 6H), l .73~1.79(m, l H), 3.67~3.69(m, 1H), 4.85(br s, 2H), 5.40~5.43(m, lH), 5.49~5.54(m, 1 H), 7.16~7.33(m, 3H)

Example 52: Synthesis of l-(2,4-dichlorophenyl)-(R)-l-hydroxyhexyl-(R)-2- carbamate(52)

The substantially same method as described in Example 1 was conducted, except that l-(2,4-dichlorophenyl)-(R,R)-l,2-(Bis-trimethylsilanyloxy)he xane (Preparation Example 99) was used instead of l-(2-chlorophenyl)-(S,S)-l ,2-(Bis-trimethylsilanyloxy) propane

(Preparation example69) to obtain the title compound (2.5g, yield 60~90%).

'H NMR(400MHz, CDCI3) 60.89(t, J= 3.6Hz, 3H), 1.28~1.42(m, 4H), 1.52~1.59(m, 1 H), 1.64- 1.71 (m, 1 H), 2.98(d, J = 5.6Hz, 1H), 4.67(br s, 2H), 4.96~5.00(m, 1H), 5.17(t, J = 5.6Hz, 1H), 7.30~7.49(m, 3H)

Example 53: Synthesis of l-(2,6-dichlorophenyl)-(R)-l-hydroxyhexyI-(R)-2- carbamate(53)

The substantially same method as described in Example 1 was conducted, except that l-(2,6-dichlorophenyl)-(R,R)-l,2-(Bis-trimethylsilanyloxy)he xane (Preparation Example 100) was used instead of l-(2-chlorophenyl)-(S,S)-l,2-(Bis-trimethylsilanyloxy) propane (Preparation example69) to obtain the title compound (2.4g, yield 60~90%).

Ή NMR(400MHz, CDC1 ₃ ) 60.84(t, J= 7.0Hz, 3H), 1.20~1.35(m, 4H), 1.36-1.41 (m, 1H), 1.59~1.63(m, 1 H), 3.71 (d, J= 10.0Hz, 1H), 4.74(br s, 2H), 5.40~5.44(m, 1 H),

5.52-5.57(m, 1H), 7.17~7.35(m, 3H)

Example 54: Synthesis of l-(2,4-dichlorophenyl)-l-hydroxypropyl-2- carbamate(54)

The substantially same method as described in Example 1 was conducted, except that l-(2,4-dichlorophenyl)- l ,2-(Bis-trimethylsilanyloxy)propane (Preparation Example 101) was used instead of l-(2-chlorophenyl)-(S,S)- l,2-(Bis-trimethylsilanyloxy) propane (Preparation example69) to obtain the title compound (1.7g, yield 60-90%).

Ή NMR(400MHz, CDC1 ₃ ) δ 1.22(d, J= 6.4Hz, 3H), 4.16(br t, 1H) 4.96(br t, 3H), 5.07(t, J= 4.8Hz, 1H), 7.23~7.52(m, 3H)

Example 55: Synthesis of l-(2,6-dichlorophenyl)-l-hydroxypropyl-2- carbamate(55)

The substantially same method as described in Example 1 was conducted, except that l -(2,6-dichlorophenyl)-l ,2-(Bis-trimethylsilanyloxy)propane (Preparation Example 102) was used instead of l-(2-chlorophenyl)-(S,S)-l,2-(Bis-trimethylsilanyloxy) propane (Preparation example69) to obtain the title compound (2.4g, yield 60-90%).

Ή NMR(400MHz, CDCl ₃ ) 61.15(d, J= 6.4Hz, 3H), 3.66(d, J = 9.2 Hz, 1H), 4.73(br s, 2H), 5.43(t, J= 9.0Hz, 1H), 5.62~5.69(m, 1 H), 7.18~7.22(m, 3H),

Example 56: Synthesis of l-(2,3-dichlorophenyl)-l-hydroxypropyl-2- carbamate(56)

The substantially same method as described in Example 1 was conducted, except that l -(2,3-dichlorophenyl)- l ,2-(Bis-trimethylsilanyloxy)propane (Preparation Example 103) was used instead of l -(2-chlorophenyl)-(S,S)-l,2-(Bis-trimethylsilanyloxy) propane (Preparation example69) to obtain the title compound (1.6g, yield 60-90%). Ή NMR(400MHz, CDC1 ₃ ) 51.15(d, J = 6.4Hz, 3H), 3.66(d, J = 9.2Hz, 1 H), 4.73(br s, 2H), 5.43(t, J= 9.0Hz, 1H), 5.62^5.69(m, 1H), 7.18~7.22(m, 3H),

Example 57: Synthesis of l-(2,4-dichlorophenyl)-l-hydroxybutyl-2- carbam

The substantially same method as described in Example 1 was conducted, except that l-(2,4-dichlorophenyl)-l,2-(Bis-trimethylsilanyloxy)butane (Preparation Example 104) was used instead of l-(2-chlorophenyl)-(S,S)-l,2-(Bis-trimethylsilanyloxy) propane (Preparation example69) to obtain the title compound ( 1.7g, yield 60~90%).

Ή NMR(400MHz, CDCI ₃ ) 60.96(t, J = 7.4Hz, 3H), i.58~1.74(m, 2H), 2.98(d, J = 5.6Hz, 1 H) 4.68(br s, 2H), 5.59(dt, J= 5.2, 8.8Hz, 1 H), 5.19(t, J= 5.4Hz, 1 H), 7.30~7.50(m, 3H)

Example 58: Synthesis of l-(2,6-dichlorophenyl)-l-hydroxybutyl-2- carbamate(58)

The substantially same method as described in Example 1 was conducted, except that l -(2,6-dichlorophenyl)-l ,2-(Bis-trimethylsilanyloxy)butane (Preparation Example 105) was used instead of l-(2-chlorophenyl)-(S,S)-l,2-(Bis-trimethylsilanyloxy) propane (Preparation example69) to obtain the title compound (2.4g, yield 60-90%).

Ή NMR(400MHz, CDCI ₃ ) 60.92(t, J = 7.4Hz, 3H), 1.30~1.38(m, 1H), 1.57~1.64(m, 1H), 3.74(d, J= 9.2Hz, 1H), 4.80(br s, 2H), 5.40~5.50(m, 2H), 7.17~7.34(m, 3H) Example 59: Synthesis of l-(2,4-dichlorophenyl)-l-hydroxy-3-methyl-butyl-2- carbamate(59)

The substantially same method as described in Example 1 was conducted, except that 1 -(2,4-dichlorophenyl)-3 -methyl- 1 ,2-(Bis-trimethylsilanyloxy)butane (Preparation Example 106) was used instead of l-(2-chlorophenyl)-(S,S)-l ,2-(Bis-trimethylsilanyloxy) propane (Preparation example69) to obtain the title compound (1.9g, yield 60-90%).

Ή NMR(400MHz, CDC1 ₃ ) 61.00(t, J = 7.2Hz, 6H), 1.73~1.79(m, 1H), 3.67~3.69(m, 1H), 4.85(br s, 2H), 5.40~5.43(m, 1 H), 5.49~5.54(m, 1 H), 7.30~7.50(m, 3H)

Example 60: Synthesis of l-(2,6-dichlorophenyl)-l-hydroxy-3-methyl-butyl-2- carbamate(60)

The substantially same method as described in Example 1 was conducted, except that l-(2,6-dichlorophenyl)-3-methyl-l ,2-(Bis-trimethylsilanyloxy)butane (Preparation Example 107) was used instead of l-(2-chlorophenyl)-(S,S)-l,2-(Bis-trimethylsilanyloxy) propane (Preparation example69) to obtain the title compound (1.7g, yield 60-90%).

Ή NMR(400MHz, CDC1 ₃ ) 61.00(t, J= 7.2Hz, 6H), 1.73-1.79(m, 1H), 3.67~3.69(m, 1 H), 4.85(br s, 2H), 5.40~5.43(m, 1H), 5.49-5.54(m, 1H), 7.16~7.33(m, 3H)

Example 61: Synthesis of l-(2,4-dichlorophenyl)-l-hydroxyhexyl-2- carbamate(61)

The substantially same method as described in Example 1 was conducted, except that l -(2,4-dichlorophenyl)-l,2-(Bis-trimethylsilanyloxy)hexane (Preparation Example 108) was used instead of 1 -(2-chlorophenyl)-(S,S)- 1 ,2-(Bis-trimethylsilanyloxy) propane (Preparation example69) to obtain the title compound (2.6g, yield 60-90%). ' H NMR(400MHZ, CDC1 ₃ ) 60.89(t, J= 3.6 Hz, 3H), 1 .28~1.42(m, 4H), 1.52~1.59(m, 1H), 1.64-1.71 (m, l H), 2.98(d, J= 5.6Hz, 1H), 4.67(br s, 2H), 4.96~5.00(m, 1H), 5.17(t, J = 5.6Hz, l H), _. 7.30~7.49(m, 3H)

Example 62: Synthesis of l-(2,6-dichlorophenyl)-l-hydroxyhexyl-2- carbam

- The substantially same method as described in Example 1 was conducted, except that l-(2,6-dichlorophenyl)-l,2-(Bis-trimethylsilanyloxy)hexane (Preparation Example 109) was used instead of l -(2-chlorophenyl)-(S,S)-l ,2-(Bis-trimethylsilanyloxy) propane (Preparation example69) to obtain the title compound (2.5g, yield 60~90%).

Ή NMR(400MHz, CDC1 ₃ ) 60.84(t, J = 7.0Hz, 3H), 1.20~l ^' .35(m, 4H), 1.36~1.41 (m, 1H), 1.59~1.63(m, 1H), 3.71(d, J= 10.0Hz, 1H), 4.74(br s, 2H), 5.40~5.44(m, 1H),

5.52~5.57(m, lH), 7.17~7.35(m, 3H)

Example 63: Synthesis of l-(2-fluorophenyl)-(S)-l-hydroxypropyl-(S)-2- carbamate(63)

The substantially same method as described in Example 1 was conducted, except that l -(2-fluorophenyl)-(S,S)-l ,2-(Bis-trimethylsilanyloxy)propane (Preparation Example 110) was used instead of l-(2-chlorophenyl)-(S,S)-l ,2-(Bis-trimethylsilanyloxy) propane (Preparation example69) to obtain the title compound (1.8g, yield 60-90%).

Ή NMR(400MHz, CDC1 ₃ ) 51.19(d, J=5.2Hz, 3H), 2.93(d, J=4.4Hz, 1 H), 4.71(br s, 2H), 4.99-5.06(m, H), 7.04~7.48(m, 4H)

Example 64: Synthesis of l-(2-fluorophenyl)-(R)-l-hydroxypropyl-(R)-2- carbamate(64)

The substantially same method as described in Example 1 was conducted, except that l-(2-fluorophenyl)-(R,R)- l,2-(Bis-trimethylsilanyloxy)propane (Preparation Example 1 1 1) was used instead of l-(2-chlorophenyl)-(S,S)-l ,2-(Bis-trimethylsilanyloxy) propane (Preparation example69) to obtain the title compound (1.6g, yield 60-90%).

Ή NMR(400MHz, CDC1 ₃ ) 61.19(d, J=5.2Hz, 3H), 2.93 (d, J=4.4Hz, IH), 4.71 (br s, 2H), 4.99~5.06(m, H), 7.04~7.48(m, 4H)

Example 65: Synthesis of l-(2-iodophenyI)-(S)-l-hydroxypropyl-(S)-2- carbamate(65)

The substantially same method as described in Example 1 was conducted, except that l -(2-iodophenyl)-(S,S)-l ,2-(Bis-trimethylsilanyloxy)propane (Preparation Example 112) was used instead of l-(2-chlorophenyl)-(S,S)-l,2-(Bis-trimethylsilanyloxy) propane (Preparation example69) to obtain the title compound (2.2g, yield 60-90%).

Ή NMR(400MHz, CDC1 ₃ ) 51.27(d, J=6.4Hz, 3H), 3.09(br s, IH), 4.83(br s, 2H), 5.00-5.10(m, 2H), 7.00~7.76(m, 4H)

Example 66: Synthesis of l-(2-iodophenyl)-(R)-l-hydroxypropyl-(R)-2- carbamate(66)

The substantially same method as described in Example 1 was conducted, except that l-(2-iodophenyl)-(R,R)- l ,2-(Bis-trimethylsilanyloxy)propane (Preparation Example 113) was used instead of l-(2-chlorophenyl)-(S,S)-l ,2-(Bis-trimethylsilanyloxy) propane (Preparation example69) to obtain the title compound (1.7g, yield 60-90%).

Ή NMR(400MHz, CDC1 ₃ ) 51.27(d, J=6.4Hz, 3H), 2.95(d, J=3.6Hz, IH), 4.73(br s, 2H), 5.01-5. l l(m, 2H), 7.01~7.86(m, 4H) Example 67: Synthesis of l-(2-iodophenyl)-(S)-l-hydroxybutyl-(S)-2- carbaniate(67)

The substantially same method as described in Example 1 was conducted, except that l-(2-iodophenyl)-(S,S)-l,2-(Bis-trimethylsilanyloxy)butane (Preparation Example 114) was used instead of l-(2-chlorophenyl)-(S,S)-l,2-(Bis-trimethylsilanyloxy) propane (Preparation example69) to obtain the title compound (2.1g, yield 60-90%).

Ή NMR(400MHz, CDC1 ₃ ) 61.27(d, J=6.4Hz, 3H), 3.09(br s, 1H), 4.83(br s, 2H), 5.00-5.10(m, 2H), 7.00-7.76(m, 4H)

Example 68: Synthesis of l-(2-chlorophenyl)-(S)-2-hydroxypropyl-(S)-l- carbamate(68)

l-(2-chlorophenyl)-(S,S)-l,2-propanediol(2.33g, Preparation example 14) obtained in Preparation Example 14, tetrahydrofuran (THF, 12ml), and carbonyldiimidazole (CDI, 3.04g) were put into a flask and stirred at the room temperature. After approximately 3 hours, ammonia solution (NH4OH, 4ml) was added thereto. When the reaction was completed, the obtained product was washed with 1 M HCl solution and ethylacetate (EA). The separated organic layer was dehydrated with anhydrous magnesium sulfate (MgS0 ₄ ), filtrated, and concented under reduced pressure. The concentrated residue was purified by a silica gel column chromatography, to obtain the title compound (0.28g, yield 10-30%).

Ή NMR(400MHz, CDC1 ₃ ) 8 l .24(d, J = 6.8Hz, 3H), 2. l3(d, J = 4.4Hz, 1 H),

4.12~4.16(m, 1H), 4.85(br s, 2H), 5.98(d, J = 5.6Hz, 1 H), 7.24~7.43(m, 4H)

Example 69: Synthesis of l-(2-chlorophenyl)-(R)-2-hydroxypropyl-(R)-l- carbamate(69)

The substantially same method as described in Example 68 was conducted, except that l-(2-chlorophenyl)-(R,R)-l,2-propanediol (Preparation Example 15) was used instead of l-(2-chlorophenyl)-(S,S)-l ,2-propanediol (Preparation example 14) to obtain the title compound (0.77g, yield 16%).

Ή NMR(400MHz, CDC1 ₃ ) 6l .24(d, J= 6.4Hz, 3H), 2.04(d, J= 4.8Hz, 1H), 4.1 1~4.18(m, 1H), 4.74(br s, 2H), 6.00(d, J = 5.6Hz, 1 H), 7.24~7.43(m, 4H)

Example 70: Synthesis of l-(2-chlorophenyl)-2-hydroxypropyl-l-carbamate(70)

The substantially same method as described in Example 68 was conducted, except that l -(2-chlorophenyl)-(R,R)-l,2-propanediol (Preparation Example 16) was used instead of l-(2-chlorophenyl)-(S,S)-l,2-propanediol (Preparation example 14) to obtain the title compound (0.16g, yield 10-30%).

Ή NMR(400MHz, CDC1 ₃ ) 61.24(d, J = 6.4Hz, 3H), 2.04(d, J = 4.8Hz, lH), 4.11~4.18(m, 1H), 4.74(br s, 2H), 6.00(d, J= 5.6Hz, lH), 7.24~7.43(m, 4H)

Example 71: Synthesis of l-(2-chlorophenyl)-(S)-2-hydroxypropyl-(S)-l- N- methylcarbamate(71)

A regioisomer of monocarbamate was separated and purified by conducting the silica gel column chromatography as described in Example 15, to obtain the title compound (0.70g, yield 10-30%).

Ή NMR(400MHz, CDC1 ₃ ) 61.21(d, J=6.4Hz, 3H), 2.80(d, J=4.8Hz, 3H), 3.12(s, 1 H), 4.09~4.16(m, 1H), 4.86(br s, 1 H), 5.99(d, J= 6.0Hz, 1H), 7.23~7.40(m, 4H) Example 72: Synthesis of l-(2-chlorophenyl)-(R)-2-hydroxypropyl-(R)-l- N- methylcarbamate 2)

A regioisomer of monocarbamate was separated and purified by conducting the silica gel column chromatography as described in Example 22, to obtain the title compound (0.69g, yield 10-30%).

Ή NMR(400MHz, CDC1 ₃ ) 51.21(d, J=6.4Hz, 3H), 2.80(d, J=4.8Hz, 3H), 3.12(s, IH), 4.09~4.16(m, IH), 4.86(br s, IH), 5.99(d, J= 6.0Hz, IH), 7.23~7.40(m, 4H)

Example 73: Synthesis of l-(2-chlorophenyl)-2-hydroxypropyl-l- N- methylcarbamate(73)

A regioisomer of monocarbamate was separated and purified by conducting the silica gel column chromatography as described in Example 29, to obtain the title compound (0.73g, yield 10-30%).

Ή NMR(400MHz, CDC1 ₃ ) δ 1.22(d, J=6Hz, 3H), 2.15(d, J=4Hz, IH), 2.81 (d, J=5Hz, 3H), 4.12(dd, J=6Hz, I H), 4.83(br s, I H), 6.00(d, J=6Hz, I H), 7.23~7.41(m, 4H)

Example 74: Synthesis of l-(2-chlorophenyl)-(S)-2-hydroxypropyl-(S)-l- N- propylcarbamate(74)

A regioisomer of monocarbamate was separated and purified by conducting the silica gel column chromatography as described in Example 16, to obtain the title compound (0.15g, yield 10-30%). Ή NMR(400 Hz, CDC1 ₃ ) δ 0.9l(t, J=7Hz, 3H), 1.22(d, J=6Hz, 3H), 1.52(dd, J=7Hz, 2H), 2.23(d, J=4Hz, 1 H), 3.09-3.2 l(m, 2H), 4.09-4.17(m, l H), 4.93(s, 1H), 5.99(d, J=6Hz, 1 H), 7.23~7.47(m, 4H) Example 75: Synthesis of l-(2-chlorophenyl)-(R)-2-hydroxypropyl-(R)-l- N- propylcarbamate(75)

A regioisomer of monocarbamate was separated and purified by conducting the silica gel column chromatography as described in Example 23, to obtain the title compound (0.04g, yield 10-30%).

Ή NMR(400MHz, CDC1 ₃ ) δ 0.91(t, J=7Hz, 3H), 1.22(d, J=6Hz, 3H), 1.52(dd, J=7Hz, 2H), 2.23(d, J=4Hz, 1H), 3.09~3.21 (m, 2H), 4.09-4.17(m, 1 H), 4.93(s, I H), 5.99(d, J=6Hz, 1H), 7.23~7.47(m, 4H)

Example 76: Synthesis of l-(2-chlorophenyl)-2-hydroxypropyl-l- propylcarbamate(76)

A regioisomer of monocarbamate was separated and purified by conducting the silica gel column chromatography as described in Example 30, to obtain the title compound (0.15g, yield 10-30%).

Ή NMR(400MHz, CDCI3) δ 0.9 l(t, J=7Hz, 3H), 1.22(d, J=6Hz, 3H), 1.52(dd, J=7Hz, 2H), 2.23(d, J=4Hz, 1H), 3.09~3.21(m, 2H), 4.09~4.17(m, 1H), 4.93(s, 1 H), 5.99(d, J=6Hz, 1 H), 7.23~7.47(m, 4H) Example 77: Synthesis of l-(2-chlorophenyl)-(S)-2-hydroxypropyl-(S)-l- N- isopropylcarbamate(77)

A regioisomer of monocarbamate was separated and purified by conducting the silica gel column chromatography as described in Example 17, to obtain the title compound (0.42g, yield 10-30%).

Ή NM (400MHz, CDC1 ₃ ) δ 1.10(d, J=6.0Hz, 3H), 1.15~1.19(m, 6H), 2.41(s, 1 H),

3.76~4.08(m, 1H), 4.34(s, 1 H), 4.83(br s 1 H), 5.95(d, J=5.3Hz, 1H), 7.19~7.39(m, 4H)

Example 78: Synthesis of l-(2-chlorophenyl)-(R)-2-hydroxypropyl-(R)-l- N- isopropylcarbamate(78)

A regioisomer of monocarbamate was separated and purified by conducting the silica gel column chromatography as described in Example 24, to obtain the title compound (0.5g, yield 10-30%).

Ή NMR(400MHz, CDC1 ₃ ) 51.13(d, J=6Hz, 3H), 1.20(dd, J=9.2Hz, 6H), 2.23(s, 1H), 3.77~3.82(m, 1 H), 4.10(s, 1H), 4.76(br s, 1 H), 5.98(d, J=5.6Hz, 1H), 7.23~7.41 (m, 4H)

Example 79: Synthesis of l-(2-chlorophenyl)-2-hydroxypropyl-l- N- isoprop lcarbamate(79)

A regioisomer of monocarbamate was separated and purified by conducting the silica gel column chromatography as described in Example 31 , to obtain the title compound (0.09g, yield 10-30%).

Ή NMR(400MHz, CDC1 ₃ ) δ 1.14(d, J=6Hz, 3H), 1.21 (dd, J=6Hz, 6H), 2.16(d, J=5Hz, 1 H), 3.81 (t, J=6Hz, 1H), 4.11(d, J=5Hz, 1 H), 4.73(br s, 1H), 5.98(d, J=5Hz, 1 H), 7.24-74 l(m, 4H) Example 80: Synthesis of l-(2-chlorophenyl)-(S)-2-hydroxypropyl-(S)-l- N- cyclopropylcarbamate(80)

A regioisomer of monocarbamate was separated and purified by conducting the silica gel column chromatography as described in Example 18, to obtain the title compound (0.53g, yield 10-30%).

Ή NMR(400MHz, CDC1 ₃ ) 60.53~0.60(m, 2H), 0.74(s, 2H), 1.21 (d, J=6.0Hz, 3H), 2.19(s, 1H), 2.59(s, 1 H), 4.11~4.15.(m, 1H), 5.13(br s, 1H), 5.99(d, J=5.20Hz, 1 H), 7.23~7.40(m, 4H)

Example 81 : Synthesis of l-(2-chlorophenyl)-(R)-2-hydroxypropyl-(R)-l- N- cyclopropylcarbamate(81)

A regioisomer of monocarbamate was separated and purified by conducting the silica gel column chromatography as described in Example 25, to obtain the title compound (0.58g, yield 10%).

Ή N R(400MHz, CDC1 ₃ ) 50.53~0.60(m, 2H), 0.74(s, 2H), 1.21(d, J=6.0Hz, 3H), 2.19(s, 1H), 2.59(s, 1H), 4.11~4.15(m, 1H), 5.13(br s, 1 H), 5.99(d, J=5.20Hz, 1H), 7.23~7.40(m, 4H)

Example 82: Synthesis of l-(2-chlorophenyl)-2-hydroxypropyl-l- N- cyclopropylcarbamate(82)

A regioisomer of monocarbamate was separated and purified by conducting the silica gel column chromatography as described in Example 32, to obtain the title compound (0.38g, yield 14%),

Ή NMR(400MHz, CDC1 ₃ ) δ 0.71(s, 2H), 1.19(d, J=6Hz, 3H), 2.45(S, IH), 2.57(S, I H), 4.08~4.12(m, IH), 5.26(s, IH), 5.97(d, J=4Hz, IH), 7.22~7.54(m, 4H) Example 83: Synthesis of l-(2-chlorophenyl)-(S)-2-hydroxypropyl-(S)-l- N- cyclohexylcarbamate(83)

A regioisomer of monocarbamate was separated and purified by conducting the silica gel column chromatography as described in Example 19, to obtain the title compound (0.24g, yield 10-30%).

Ή NMR(400 Hz, CDCI ₃ ) δ1.10~1.39(ηι, 7H), 1.61(s, 3H), 1.71~1.74(m, 2H), 1.87(d, J=11.2Hz, IH), 2.48(d, J=10.8Hz, I H), 3.46(t, J=4Hz, IH), 4.10~4.11(m, IH), 4.80(br s IH), 5.97(d, J=5.6Hz, IH), 7.23~7.41(m, 4H)

Example 84: Synthesis of l-(2-chlorophenyl)-(R)-2-hydroxypropyl-(R)-l- cyclohexylcarbamate(84)

A regioisomer of monocarbamate was separated and purified by conducting the silica gel column chromatography as described in Example 26, to obtain the title compound (0.35g, yield 10%).

Ή N R(400MHz, CDC1 ₃ ) 61.10~1.39(m, 7H), 1.61(s, 3H), 1.71~1.74(m, 2H), 1.87(d, J=11.2Hz, IH), 2.48(d, J=10.8Hz, IH), 3.46(t, J=4Hz, IH), 4.10~4.11(m, IH), 4.80(br s IH), 5.97(d, J=5.6Hz, I H), 7.23~7.4l(m, 4H) Example 85: Synthesis of l-(2-chlorophenyl)-2-hydroxypropyl-l- N- cyclohexylcarbamate(85)

A regioisomer of monocarbamate was separated and purified by conducting the silica gel column chromatography as described in Example 33, to obtain the title compound (0.26g, yield 10%).

Ή NMR(400MHz, CDC1 ₃ ) δ 1.12-1.19(m, 3H), 1.22(d, J=6Hz, 3H), 1.27~1.37(m, 1H), 1.71(t, J=6Hz, 2H), 1.86-1.88(m, 1 H), 1.97~2.00(m, 1 H), 2.18(d, J=4Hz, 1H), 3.47(S, 1 H), 4.12(t, J=6Hz, 1H), 4.78(S, 1H), 5.97(d, J=6Hz, 1H), 7.23~7.40(m, 4H)

Example 86: Synthesis of l-(2-chlorophenyl)-(S)-2-hydroxypropyl-(S)-l- N- benzylcarbamate(86)

A regioisomer of monocarbamate was separated and purified by conducting the silica gel column chromatography as described in Example 20, to obtain the title compound (0.19g, yield 10-30%).

Ή NMR(400MHz, CDC1 ₃ ) δ 1.23(d, J=6Hz, 3H), 2.16(d, J=4Hz, 1H), 4.12(t, J=6Hz, 1 H), 4.3 l~4.44(m, 2H), 5.22(br S, 1H), 6.04(d, J=6Hz, 1H), 7.27~7.42(m, 9H)

Example 87: Synthesis of l-(2-chlorophenyl)-(R)-2-hydroxypropyl-(R)-l- N- benzylcarbamate(87)

A regioisomer of monocarbamate was separated and purified by conducting the silica gel column chromatography as described in Example 27, to obtain the title compound (0.07g, yield 10-30%).

Ή NMR(400MHz, CDC1 ₃ ) δ 1.23(d, J=6Hz, 3H), 2.16(d, J=4Hz, 1H), 4.12(t, J=6Hz, l H), 4.3 l~4.44(m, 2H), 5.22(br S, 1H), 6.04(d, J=6Hz, 1H), 7.27~7.42(m, 9H) Example 88: Synthesis of l-(2-chlorophenyl)-2-hydroxypropyl-l- N- benzylcarbamate(88)

A regioisomer of monocarbamate was separated and purified by conducting the silica gel column chromatography as described in Example 34, to obtain the title compound (( 21g, yield 14%).

H NMR(400MHz, CDC1 ₃ ) δ 1.23(d, J=6Hz, 3H), 2.16(d, J=4Hz, IH), 4.12(t, J=6Hz, 1H), 4.31~4.44(m, 2H), 5.22(br S, 1H), 6.04(d, J=6Hz, IH), 7.27~7.42(m, 9H)

Example 89: Synthesis of l-(2,4-dichlorophenyl)-(S)-2-hydroxypropyl-(S)-l- carbamate(89)

The substantially same method as described in Example 68 was conducted, except that l-(2,4-dichlorophenyl)-(S,S)-l,2-propanediol(Preparation example 26)was used instead of l-(2-chlorophenyl)-(S,S)- l,2-propanediol(Preparation example 14), to obtain the title compound (0.05g, yield 10-30%).

' H NMR(400MHZ, CDCl ₃ ) 6 l . l 3(d, J= 6.8Hz, 3H), 2.49(d, J= 4.0Hz, 1 H),

4.66~4.74(m, 1H), 4.76(br s, 2H), 6.20(d, J= 8.8Hz, I H), 7.30(d, J=8.4Hz, 1H), 7.39(d, J=2.0Hz, 2H), 7.50(dd, J=8.4Hz, 2.0Hz, 1 H)

Example 90: Synthesis of l-(2,6-dichlorophenyI)-(S)-2-hydroxypropyl-(S)-l- carbamate(90)

The substantially same method as described in Example 68 was conducted, except that l -(2,6-dichlorophenyl)-(S,S)-l,2-propanediol(Preparation example 38)was used instead of l-(2-chlorophenyl)-(S,S)-l,2-propanediol(Preparation example 14), to obtain the title compound (0.07g, yield 24%).

Ή NMR(400MHz, CDC1 ₃ ) δ ΐ . I3(d, J= 6.8Hz, 3H), 2.49(d, J= 4.0Hz, IH), 4.66~4.74(m, 1H), 4.76(br s, 2H), 6.20(d, J = 8.8Hz, 1H), 7.25~7.40(m, 3H)

Example 91: Synthesis of l-(2,3-dichlorophenyl)-(S)-2-hydroxypropyl-(S)-l- carbamate(91)

The substantially same method as described in Example 68 was conducted, except that l -(2,3-dichlorophenyl)-(S,S)- l ,2-propanediol(Preparation example 57)was used instead of l-(2-chlorophenyl)-(S,S)-l,2-propanediol(Preparation example 14), to obtain the title compound (0.08g, yield 10-30%).

Ή NMR(400MHz, CDC1 ₃ ) 6 l . l 5(d, J= 6.4Hz, 3H), 3.66(d, J= 9.2Hz, 1H), 4.73(br s, 2H), 5.43(t, J= 9.0Hz, 1 H), 5.62~5.69(m, 1H), 7.18~7.22(m, 3H),

Example 92: Synthesis of l-(2,4-dichlorophenyl)-(S)-2-hydroxybutyl-(S)-l- carbamate(92)

The substantially same method as described in Example 68 was conducted, except that l-(2,4-dichlorophenyl)-(S,S)-l ,2-butanediol(Preparation example 29)was used instead of l-(2-chlorophenyl)-(S,S)- l ,2-propanediol(Preparation example 14), to obtain the title compound (0.07g, yield 10-30%).

'H NMR(400MHZ, CDCl ₃ ) 80.77(t, J= 7.4Hz, 3H), 0.92-1.01 (m, I H), 1. 18~1.28(m, 1H), 4.06-4.13(m, I H), 4.96(d, J= 6.0Hz, 1H), 5.91(d, J= 8.8Hz, 1H), 6.4(br s, 2H), 7.30-7.50(m, 3H) Example 93: Synthesis of l-(2,6-dichlorophenyl)-(S)-2-hydroxybutyl-(S)-l- carbamate(93)

The substantially same method as described in Example 68 was conducted, except that l -(2,6-dichlorophenyl)-(S,S)-l,2-butanediol(Preparation example 41)was used instead of l-(2-chlorophenyl)-(S,S)-l ,2-propanediol(Preparation example 14), to obtain the title compound (0.1 1 g, yield 29%).

1H NMR(400MHz, CDCl ₃ ) 60.77(t, J= 7.4Hz, 3H), 0.92-1.01 (m, 1H), 1.18~1.28(m, lH), 4.06-4.13(m, 1H), 4.96(d, J=6.0Hz, IH), 5.91 (d, J=8.8Hz, lH), 6.4(br s, 2H),

7.25~7.40(m, 3H)

Example 94: Synthesis of l-(2,4-dichlorophenyl)-(S)-2-hydroxy-3-methyl-butyl- (S)-l-carbamate(94)

The substantially same method as described in Example 68 was conducted, except that l-(2,4-dichlorophenyl)-3-methyl-(S,S)-l,2-butanediol(Prepara tion example 32)was used instead of l-(2-chlorophenyl)-(S,S)-l,2-propanediol(Preparation example 14), to obtain the title compound (O.O g, yield 10-30%).

Ή NMR(400MHz, CDC1 ₃ ) 61.00(t, J= 7.2Hz, 6H), 1.73~1.79(m, 1 H), 3.67~3.69(m, 1 H), 4.96(d, J=6.0Hz, I H), 5.9 l (d, J=8.8Hz, 1H), 6.42(br s, 2H), 7.30~7.50(m, 3H)

Example 95: Synthesis of l-(2,6-dichlorophenyl)-(S)-2-hydroxy-3-methyl-butyI- (S)-l-carbamate(95)

W 201

The substantially same method as described in Example 68 was conducted, except that l-(2,6-dichlorophenyl)-3-methyl-(S,S)-l ,2-butanediol(Preparation example 44)was used instead of l-(2-chlorophenyl)-(S,S)-l,2-propanediol(Preparation example 14), to obtain the title compound (0.03g, yield 10-30%).

Ή NMR(400MHz, CDC1 ₃ ) 61.00(t, J = 7.2Hz, 6H), 1.73~1.79(m, lH), 3.67~3.69(m, 1H), 4.96(d, J=6.0Hz, 1H), 5.91 (d, J=8.8Hz, 1H), 6.42(br s, 2H), 7.25~7.40(m, 3H)

Example 96: Synthesis of l-(2,4-dichlorophenyl)-(S)-2-hydroxyhexyl-(S)-l- carbamate(96)

The substantially same method as described in Example 68 was conducted, except that l-(2,4-dichlorophenyl)-(S,S)- l ,2-hexanediol(Preparation example 35)was used instead of l-(2-chlorophenyl)-(S,S)-l,2-propanediol(Preparation example 14), to obtain the title compound (0.21 g, yield 10-30%).

Ή NMR(400MHz, CDC1 ₃ ) 60.85(t, J=7.2Hz, 3H), 1.18-1.33(m, 4H), 1.48-1.55(m, 2H), 2.35(d, J=4.4Hz, 1H), 4.45~4.50(m, 1 H), 4.76(br s, 2H), 6.2 l (d, J=8.4Hz, 1 H),

7.30~7.50(m, 3H)

Example 97: Synthesis of l-(2,6-dichlorophenyl)-(S)-2-hydroxyhexyl-(S)-l- carbamate(97)

The substantially same method as described in Example 68 was conducted, except that l-(2,6-dichlorophenyl)-(S,S)- l ,2-hexanediol(Preparation example 47)was used instead of l-(2-chlorophenyl)-(S,S)-l,2-propanediol(Preparation example 14), to obtain the title compound (0.06g, yield 29%). 'H NMR(400MHz, CDCI3) 50.85(t, J= 7.2Hz, 3H), 1.18~1.33(m, 4H), 1.48~1.55(m, 2H), 2.35(d, J = 4.4Hz, 1H), 4.45 4.50(m, 1 H), 4.76(br s, 2H), 6.21(d, J=8.4Hz, 1H), 7.16~7.34(m, 3H)

Example 98: Synthesis of l-(2,4-dichlorophenyl)-(R)-2-hydroxypropyl-(R)-l- carbamate(98)

The substantially same method as described in Example 68 was conducted, except that l-(2,4-dichlorophenyl)-(R,R)-l,2-propanediol(Preparation example 27)was used instead of l-(2-chlorophenyl)-(S,S)-l,2-propanediol(Preparation example 14), to obtain the title compound (0.04g, yield 10-30%).

Ή NMR(400MHz, CDC1 ₃ ) 61.13(d, J=6.8Hz, 3H), 2.49(d, J=4.0Hz, 1H),

4.66~4.74(m, 1H), 4.76(br s, 2H), 6.20(d, J=8.8Hz, 1H), 7.30~7.50(m, 3H)

Example 99: Synthesis of l-(2,6-dichlorophenyl)-(R)-2-hydroxypropyl-(R)-l- carbamate(99)

The substantially same method as described in Example 68 was conducted, except that l-(2,6-dichlorophenyl)-(R,R)-l,2-propanediol(Preparation example 39)was used instead of l-(2-chlorophenyl)-(S,S)- l ,2-propanediol(Preparation example 14), to obtain the title compound (0.09g, yield 10-30%).

Ή NMR(400MHz, CDC1 ₃ ) 61.13(d, J = 6.8Hz, 3H), 2.49(d, J= 4.0Hz, 1H),

4.66~4.74(m, 1H), 4.76(br s, 2H), 6.20(d, J = 8.8Hz, 1H), 7.25~7.40(m, 3H)

Example 100: Synthesis of l-(2,3-dichlorophenyl)-(R)-2-hydroxypropyl-(R)-l- carbamate(lOO)

The substantially same method as described in Example 68 was conducted, except that l-(2,3-dichlorophenyl)-(R,R)-l,2-propanediol(Preparation example 58)was used instead of l-(2-chlorophenyl)-(S,S)-l,2-propanediol(Preparation example 14), to obtain the title compound (0.25g, yield 10-30%).

Ή NMR(400MHz, CDC1 ₃ ) 5l.l5(d,J = 6.4Hz, 3H), 3.66(d,J= 9.2Hz, 1H), 4.73(br s, 2H), 5.43(t,J= 9.0Hz, 1H), 5.62~5.69(m, 1H), 7;18~7.22(m, 3H),

Example 101: Synthesis of l-(2,4-dichlorophenyl)-(R)-2-hydroxybutyl-(R)-l- carbamate(lOl)

The substantially same method as described in Example 68 was conducted, except that l-(2,4-dichlorophenyl)-(R,R)-l,2-butanediol(Preparation example 30)was used instead of l-(2-chlorophenyl)-(S,S)-l,2-propanediol(Preparation examplel4), to obtain the title compound (0.08g, yield 10-30%).

Ή NMR(400MHz, CDC1 ₃ ) 60.77(t, J= 7.4Hz, 3H), 0.92~1.01(m, 1H), 1.18-1.28(m, 1H), 4.06~4.13(m, 1H), 4.96(d, J= 6.0Hz, 1H), 5.91(d, J= 8.8Hz, 1H), 6.4(br s, 2H), 7.30-7.50(m, 3H) Example 102: Synthesis of l-(2,6-dichlorophenyl)-(R)-2-hydroxybutyl-(R)-l- carbamate(102)

The substantially same method as described in Example 68 was conducted, except that l-(2,6-dichlorophenyl)-(R,R)-l,2-butanediol(Preparation example 42)was used instead l-(2-chlorophenyl)-(S,S)-l,2-propanediol(Preparation example 14), to obtain the title compound (0.09g, yield 10-30%). Ή NMR(400MHz, CDC1 ₃ ) 80.77(t, J= 7.4Hz, 3H), 0.92-1.01(m, lH), 1.18~1.28(m, 1H), 4.06~4.13(m, 1H), 4.96(d, J = 6.0Hz, 1H), 5.91(d, J = 8.8Hz, 1 H), 6.4(br s, 2H), 7.25~7.40(m, 3H)

Example 103: Synthesis of l-(2,4-dichlorophenyl)-(R)-2-hydroxy-3-methyl- butyl-(R)-l-carbamate(103)

The substantially same method as described in Example 68 was conducted, except that l-(2,4-dichlorophenyl)-3-methyl-(R,R)- l ,2-propanediol(Preparation example 33)was used instead of l-(2-chlorophenyl)-(S,S)-l,2-propanediol(Preparation examplel4), to obtain the title compound (O.Olg, yield 10-30%).

Ή NMR(400MHz, CDC1 ₃ ) 61.00(t, J= 7.2Hz, 6H), 1.73~1.79(m, 1H), 3.67~3.69(m, 1H), 4.96(d, J=6.0Hz, 1H), 5.91 (d, J=8.8Hz, l H), 6.42(br s, 2H), 7.30~7.50(m, 3H)

Example 104: Synthesis of l-(2,6-dichlorophenyl)-(R)-2-hydroxy-3-methyI- butyl-(R)-l-carbamate(104)

The substantially same method as described in Example 68 was conducted, except that l -(2,6-dichlorophenyl)-3-methyl-(R,R)-l ,2-propanediol(Preparation example 45)was used instead of l-(2-chlorophenyl)-(S,S)-l ,2-propanediol(Preparation example 14), to obtain the title compound (0.01 g, yield 10-30%).

Ή NMR(400MHz, CDC1 ₃ ) 6 l .00(t, J= 7.2Hz, 6H), 1.73~1.79(m, 1 H), 3.67-3.69(m, l H), 4.96(d, J=6.0Hz, 1 H), 5.91 (d, J=8.8Hz, 1H), 6.42(br s, 2H), 7.25~7.40(m, 3H)

Example 105: Synthesis of l-(2,4-dichIorophenyl)-(R)-2-hydroxyhexyl-(R)-l- carbamate(105)

The substantially same method as described in Example 68 was conducted, except that l-(2,4-dichlorophenyl)-(R, )-l ,2-hexanediol(Preparation example 36)was used instead of l-(2-chlorophenyl)-(S,S)-l ,2-propanediol(Preparation example 14), to obtain the title compound (0.2 l g, yield 10-30%).

Ή NMR(400MHz, CDC1 ₃ ) 60.85(t, J=7.2Hz, 3H), 1.18~1.33(m, 4H), 1.48~1.55(m, 2H), 2.35(d, J=4.4Hz, 1 H), 4.45~4.50(m, 1 H), 4.76(br s, 2H), 6.21(d, J=8.4Hz, 1H), 7.30~7.50(m, 3H) Example 106: Synthesis of l-(2,6-dichlorophenyl)-(R)-2-hydroxyhexyl-(R)-l- carbamate(106)

The substantially same method as described in Example 68 was conducted, except that l-(2,6-dichlorophenyl)-(R,R)-l,2-hexanediol(Preparation example 48)was used instead of l-(2-chlorophenyl)-(S,S)-l,2-propanediol(Preparation example 14), to obtain the title compound (0.12g, yield 10-30%).

'H NMR(400MHz, CDC1 ₃ ) 60.85(t, J= 7.2Hz, 3H), 1.18~1.33(m, 4H), 1.48-1.55(m, 2H), 2.35(d, J = 4.4Hz, 1H), 4.45~4.50(m, 1H), 4.76(br s, 2H), 6.2 l(d, J= 8.4Hz, 1 H), 7.16~7.34(m, 3H)

Example 107: Synthesis of l-(2,4-dichlorophenyl)-2-hydroxypropyl-l- carbamate(107)

The substantially same method as described in Example 68 was conducted, except that l -(2,4-dichlorophenyl)- l,2-propanediol(Preparation example 28)was used instead of 1- (2-chlorophenyl)-(S,S)-l,2-propanediol(Preparation example 14), to obtain the title compound (0.05g, yield 10-30%).

Ή NMR(400MHz, CDC1 ₃ ) 61.13(d, J=6.8Hz, 3H), 2.49(d, J=4.0Hz, 1H),

4.66~4.74(m, 1H), 4.76(br s, 2H), 6.20(d, J=8.8Hz, 1 H), 7.30-7.50(m, 3H)

Example 108: Synthesis of l-(2,6-dichlorophenyl)-2-hydroxypropyl-l- carbamate(108)

The substantially same method as described in Example 68 was conducted, except that l -(2,6-dichlorophenyl)-l,2-propanediol(Preparation example 40)was used instead of 1- (2-chlorophenyl)-(S,S)-l ,2-propanediol(Preparation example 14), to obtain the title compound (0.06g, yield 10-30%).

Ή NMR(400MHz, CDC1 ₃ ) 61.13(d, J= 6.8Hz, 3H), 2.49(d, J= 4.0Hz, 1H), 4.66~4.74(m, 1H), 4.76(br s, 2H), 6.20(d, J= 8.8Hz, 1 H), 7.25~7.40(m, 3H)

Example 109: Synthesis of l-(2,3-dichlorophenyl)-(R)-2-hydroxypropyl-(R)-l- carbamate(109)

The substantially same method as described in Example 68 was conducted, except that l-(2,3-dichlorophenyl)-l ,2-propanediol(Preparation example 59)was used instead of 1 - (2-chlorophenyl)-(S,S)-l ,2-propanediol(Preparation example 14), to obtain the title compound (0.02g, yield 10-30%).

Ή NMR(400MHz, CDC1 ₃ ) δ 1. 15(d, J= 6.4Hz, 3H), 3.66(d, J= 9.2Hz, 1H), 4.73(br s, 2H), 5.43(t, J= 9.0Hz, 1H), 5.62~5.69(m, lH), 7.18~7.22(m, 3H),

Example 110: Synthesis of l-(2,4-dichlorophenyl)-2-hydroxybutyl-l- carbamate(llO)

The substantially same method as described in Example 68 was conducted, except that l-(2,4-dichlorophenyl)-l,2-butanediol(Preparation example 31)was used instead of l-(2- chlorophenyl)-(S,S)-l,2-propanediol(Preparation example 14), to obtain the title compound (0.07g, yield 10-30%).

' H NMR(400MHZ, CDCI3) 80.77(t, J=7.4Hz, 3H), 0.92~1.01 (m, 1H), 1.18~1.28(m, 1H), 4.06~4.13(m, 1 H), 4.96(d, J=6.0Hz, 1H), 5.91 (d, J=8.8Hz, 1H), 6.4(br s, 2H),

7.30~7.50(m, 3H)

Example 111 : Synthesis of l-(2,6-dichlorophenyl)-2-hydroxybutyl-l- carbamate(lll)

The substantially same method as described in Example 68 was conducted, except that l-(2,6-dichlorophenyl)-l ,2-butanediol(Preparation example 43)was used instead of l -(2- chlorophenyl)-(S,S)-l,2-propanediol(Preparation example 14), to obtain the title compound (0.1 Og, yield 10-30%).

Ή NMR(400MHz, CDCI3) 60.77(t, J = 7.4Hz, 3H), 0.92-1.01 (m, 1H), 1.18~1.28(m, 1H), 4.06-4.13(m, 1H), 4.96(d, J = 6.0Hz, 1H), 5.91(d, J= 8.8Hz, 1H), 6.4(br s, 2H), 7.25~7.40(m, 3H) Example 112: Synthesis of l-(2,4-dichlorophenyl)-2-hydroxy-3-methyI-butyl-l- carbamate(112)

The substantially same method as described in Example 68 was conducted, except that l -(2,4-dichlorophenyl)-3-methyl- l,2-propanediol(Preparation example 34)was used instead of l-(2-chlorophenyl)-(S,S)- l ,2-propanediol(Preparation example 14), to obtain the title compound (0.04g, yield 10-30%).

lH NMR(400MHz, CDC1 ₃ ) 6 l .00(t, J= 7.2Hz, 6H), 1.73~1.79(m, IH), 3.67~3.69(m, I H), 4.96(d, J=6.0Hz, I H), 5.91(d, J=8.8Hz, IH), 6.42(br s, 2H), 7.30~7.50(m, 3H)

Example 113: Synthesis of l-(2,6-dichlorophenyl)-2-hydroxy-3-methyl-butyl-l- carbamate(113)

The substantially same method as described in Example 68 was conducted, except that l-(2,6-dichlorophenyl)-3-methyl-l,2-propanediol(Preparation example 46)was used instead of l -(2-chlorophenyl)-(S,S)-l,2-propanediol(Preparation example 14), to obtain the title compound (0.0 l g, yield 10-30%).

Ή NMR(400MHz, CDC1 ₃ ) 61.00(t, J= 7.2Hz, 6H), 1.73~1.79(m, IH), 3.67~3.69(m, IH), 4.96(d, J=6.0Hz, I H), 5.91 (d, J=8.8Hz, IH), 6.42(br s, 2H), 7.25~7.40(m, 3H)

Example 114: Synthesis of l-(2,4-dichlorophenyl)-2-hydroxyhexyl-l- carbamate(114)

The substantially same method as described in Example 68 was conducted, except that l -(2,4-dichlorophenyl)-l ,2-hexanediol(Preparation example 37)was used instead of l-(2- chlorophenyl)-(S,S)-l ,2-propanediol(Preparation example 14), to obtain the title compound (0.2 g, yield 10-30%).

Ή NMR(400MHz, CDC1 ₃ ) 60.85(t, J=7.2Hz, 3H), 1.18~1.33(m, 4H), 1.48-1.55(m, 2H), 2.35(d, J=4.4Hz, IH), 4.45~4.50(m, I H), 4.76(br s, 2H), 6.2 l (d, J=8.4Hz, IH), 7.30~7.50(m, 3H) Example 115: Synthesis of l-(2,6-dichlorophenyl)-2-hydroxyhexyl-l- carbamate(115)

The substantially same method as described in Example 68 was conducted, except that l-(2,6-dichlorophenyl)-l,2-hexanediol(Preparation example 49)was used instead of l-(2- chlorophenyl)-(S,S)-l,2-propanediol(Preparation example 14), to obtain the title compound (0.12g, yield 10-30%).

'H NMR(400MHz, CDCI ₃ ) 60.85(t, J= 7.2Hz, 3H), i. l 8~1.33(m, 4H), 1.48~1.55(m, 2H), 2.35(d, = 4.4Hz, 1H), 4.45~4.50(m, 1H), 4.76(br s, 2H), 6.2 l(d, J= 8.4Hz, 1H), 7.16~7.34(m, 3H)

Compounds 1 to 1 15 produced in Examples 1 to 1 15 were summarized in following Tables 1 and 2.

(Table 1) Compounds 1 to 67 having the structure of Chemical Formula 1 where 'A' is a carbamoyl derivative and 'B' is H

(Table 2) Compounds 68 to 1 15 having the structure of Chemical Fonnula 1 where H and 'B' is a carbamoyl derivative

Example 116: Harnialine-induced tremor model

Harmaline is a central nervous system stimulant and a "reversible inhibitor of MAO- A (RI A)". [Massaro, E. J. (2002). Handbook of Neurotoxicology. Totowa, NJ: Humana Press, p. 237]. Harmaline is known to induce 4- to 10-Hz oscillation in olivocerebellar pathways, we performed simultaneous recordings of tremor(voluntary sham startles or voluntary tonic contraction)

Experimental animal, male Sprague-Dawley rats, was purchased from OrientBio, Korea and housed 4-5 rats per cage for 4-5 days. The range of body weight was used between 130 and 160 grams. All rats were transferred to the test room 1 hour prior to the test. Rats were given the compound through oral route (p.o., 5 ml/kg). Harmaline (10 mg/kg in volume of 5 ml/kg, i.p.) was administered 1 hour thereafter. Immediately after the harmaline, rats were placed individually in a blind fashion in plastic cages and observed for 30 minutes. The period between the injection of harmaline and the appearance of the first symptom of tremor was recorded as a time of tremor onset. Since rats that exhibited tremors at rest also exhibited tremors while moving, tremors that appeared during the rest were assigned a score 2, while tremors that only appeared during the locomotion were assigned a score 1. Tremors that appeared continuously were assigned a score 2, while tremors that appeared intermittently were assigned a score 1. The appearance of generalized tremors was assigned a score 2, while a score 1 was assigned to tremor that involved only the head, body, or tail of the rat. The severity of tremor was scored was scored subjectively as mild in intensity or as moderate or marked. When the severity of tremor was considered moderate or marked, the score was assigned as described above. When the severity of tremor was considered mild, the score that was assigned was one-half of that described above. Scores for each rat were summed; the sum of the scores was compared by ranking tremor quality and severity. Statistical analysis was performed by a one-way ANOVA followed by Tukey HSD test, and Student t-test using Statistica (Statsoft Inc.) or SPSS software program (SPSS Inc.). The obtained results are shown in following Tables 3 and 4. (Reference; Martin F.C., Le A.T., and Haridforth A. (2005). Harmaline-induced tremor as a potential preclinical screening method for essential tremor medications. Mov. Disord. 20: 298-305).

(Table 3) Measurement results of anti-movement activity of 1 -(2-chlorophenyl)-(S)- l -hydroxypropyl-(S)-2-carbamate(compound 1 ) in the test(Rats)

10 mg/kg 8 2.5 . 3.6±0.6 <0.001 265 289±19 <0.01

20 mg/kg 8 1.8 1.8±0.1 <0.001 375 367±21 <0.001

(Table 4) Measurement results of anti-movement activity of compounds in the test(Rats)

a: Injection amount(mg/kg),

Protection %= the percentage of activity compared to the vehicle only.

Example 117: Anti-excitation activity using MES test

In the MES test(Ref, G. Villetti et al. Neuropharmacology 40(2001 ) 866-878), an electrical stimulus(mice; 50mA, 60Hz, 0.2sec and rats; 150mA 60Hz, 0.2sec in the test animal) supplied by 1 1A Shocker(IITC Life Science Company) was delivered through corneal electrodes. All mice assigned to any electroshock at peak time (0.25, 0.5, 1 , 2, 4hr) were treated with each test compound sample which was dissolved in 30% PEG400 or 20% Tween80 prepared by saline solvent applied to oral before the test. If the test animal stretching their hind limb in a straight line weren't observed in the MES test, the results indicate that the test sample had an anti-excitation activity. Three doses of the test sample were administered orally to over 18 mice (6 mice per dose) for evaluating the respective doses at which 50% of the animals are protected from seizure (ED50). The value of ED50 (median effective dose) is calculated by Litchfield and Wicoxon log-probit method which is a dose-response relationship. Then, the test results are shown in following Table 3. Experimental animal, male ICR mice and male SD rats, were purchased from OrientBio or Nara biotech, Korea, and housed 4-5 mice per a cage for 4-5 days. The range of mice body weight was used between 19 and 26 grams. The obtained results are shown in following Table 5.

Example 118: Neurotoxicity

The measurement of neurotoxicity of the test compounds was conducted by the method of Dunham and Miya [Dunham, N.W. and Miya, T.S. 1957. A note on a simple apparatus for detecting neurological deficit in rats and mice. J. Am. Pharm. Assoc. (Baltimore) 46: 208-209]. In the method, motor abilities of the test animals can be determined by observing whether the test animals can walk without falling from a rotator, thereby determining the value of neurotoxicity of each compound. Term "TD50" means the respective dose of the test compound at which 50% of the test animal exhibit neurotoxicity. They were pre-trained on the rotarod (Rotarod; Columbus instrument, rota-max, USA) at 6 rpm for 5 min 24 hr prior to the test. The peak time was determined by administration test material's random dose for 0.5, 1, 2, 4 hour. To evaluate the minimal neurotoxicity of the compound, the mice were placed on the Rotarod (rod circle; 3Cm) at 6rpm and the test animal fails to maintain walking once or more during 1 minute, it can be regarded that the test animal exhibits neurotoxicity. The ratio of TD50 to ED50 (TD50/ED50) is called as a protective index, and useful as a parameter for comparison of pharmaceutical efficacy and neurotoxicity. The obtained results are shown in following Table 6.

[Statistical Analysis]

The obtained results are shown as mean±sem. The difference between the groups was statistically analyzed by ANOVA, and then, further examined by Dunnett's test or Bonferroni test. If p is less than 0.05, it was determined that the difference between the groups had statistical significance.

(Table 5) Measurement results of anti-excitation activity of compounds in the test animals (Mice)

3 31.4 2

4 82.4 0.5

5 84.1 0.5

6 22.2 1

8 100 ^a (100%) -

9 67.1 0.5

12 100 ^a (75%) -

13 200 ^a (75%) -

14 200 ^a ( 100%) -

15 I00 ^a (75%) -

16 200 ^a (25%) - ^■

18 200 ^a (100%) -

23 200 ^a (25%) -

25 200 ^a (25%) -

29 200 ^a (75%) -

30 200 ^a (25%) -

31 200 ^a (25%) -

32 200 ^a ( 100%) -

36 82.8 -

37 25.8 0.25

38 91.4 2

39 41.2 1

40 46.9 -

42 35.2 0.5

43 100 ^a (25%) -

44 100 ^a (75%) -

46 35.2 1

63 50 ^a (100%) -

65 50 ^a (100%) -

67 100 ^a (100%) - a: Injection amount(mg/kg),

Protection%= the percentage of activity compared to the vehicle only, respectively. (Table 6) Measurement results of neurotoxicity of compounds in the test animals

(Mice)

Example 119: PTZ(Pentylenetetrazol) test

In this experiment, administered intraperitoneally or orally to test animals (Mouse; ICR, and Rats; SD); Experimental animal, male SD rats, were purchased from OrientBio or Nara biotech, Korea, and housed 4-5 mice per a cage for 4-5 days. The range of mice body weight was used between 19 and 26 grams and range of rats body weight was used between 100 and 130 grams. After Peak time (0.5, 1 , 2 and 4hr) from the administration, PTZ (Pentylenetetrazol) was administered subcutaneously in the concentration capable of inducing

97% intermittent convulsions (mice & rats: 90-1 10 mg/kg*bw, 2 /g). If clonic seizure was not observed for at least 3 seconds in the PTZ administered animal, it can be considered that the test compound has anti-nonconvulsive seizure activity. The median effective dose (ED50) is determined using 6 animals per a concentration (total three different concentrations), and calculated by Litchfield and Wicoxon log-probit method which is a dose-response relationship. The obtained results are shown in following Tables 7 and 8.

(Table 7) Measurement results of anti-nonconvulsive seizure activity of compounds in the test animals

5 15.0 0.5

6 17.9 0.5

8 ^a 20.4 (50%) -

9 ^a 20.4 (33.3%) -

12 ^a 20.4 (33.3%) -

13 ^a 20.4 (50%) -

14 ^a 20.4 (16.7%) -

23 ^a 20.4 (50%) -

25 ^a 20.4 (66.7%) -

29 ^a 20.4 (33.3%) -

30 ^a 20.4 (33.3%) - ^■

31 ^a 20.4 (83.3%) -

32 ^a 20.4 (16.7%) -

36 ^a 20.4 (33.3%) -

37 25.7 0.25

38 ^a 20.4 (50%) -

39 24.3 0.5

40 ^a 20.4 (33.3%) -

42 ^a 20.4 (50%) -

44 ^a 20.4 (33.3%) -

45 ^a 20.4 (16.7%) -

46 ^a 20.4 (50%) -

63 ^a 20.4 (50%) -

65 ^a 20.4 (100%) -

67 23.1 0.5

a: Injection amount (mg/kg), Protection % (Mice),

: Peak Time (h)

(Table 8) Measurement results of anti-nonconvulsive seizure activity of compounds the test animals

: ea me