Title:
PROCESS FOR PREPARING (-)-(1S,4R) N-PROTECTED 4-AMINO-2-CYCLOPENTENE-1-CARBOXYLATE ESTERS
Document Type and Number:
WIPO Patent Application WO/2001/001569
Kind Code:
A2
Abstract:
The invention relates to a process for preparing (-)-(1S,4R) N protected 4-amino-2-cylcopentene-1-carboxylate esters represented by formula (I) wherein R¿1? and R¿2? are as described within the specification.
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Inventors:
REY MAX
WELTI GREGOR
MARYANOFF CYNTHIA
WELTI GREGOR
MARYANOFF CYNTHIA
Application Number:
PCT/US2000/015969
Publication Date:
January 04, 2001
Filing Date:
June 09, 2000
Export Citation:
Assignee:
ORTHO MCNEIL PHARM INC (US)
International Classes:
C07B53/00; C07B57/00; C07C227/22; C07C229/48; C07C269/04; C07C271/24; (IPC1-7): H03H9/00
Domestic Patent References:
| WO1998024741A2 | 1998-06-11 |
Foreign References:
| EP0590685A1 | 1994-04-06 | |||
| US5399580A | 1995-03-21 |
Other References:
CHEMICAL ABSTRACTS, vol. 124, no. 13, 25 March 1996 Columbus, Ohio, US; abstract no. 175421u, TROST, B.M.: "An enantioselective syntheses of cis-4-tert-butoxycarbamoyl- -1-methoxycarbonyl-2- -cyclopentene - a useful, general building block" page 1230; column 1, XP002901396 & Chem.--Eur.J., vol. 1, no. 8, 1995, pages 568-572,
Attorney, Agent or Firm:
Ciamporcero Jr., Audley A. (NJ, US)
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Claims:
CLAIMS What is Claimed:
| 1. | A process for preparing a Compound of formula (I) wherein R1 and R2 are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, substituted aryl and aralkyl; comprising reacting () 2azabicyclo [2.2.1] hept5en3one of formula (II) with an alcohol of formula (III), R1OH, wherein Ru ils as described above, and a nonaqueous acid, to form the corresponding Compound of formula (IV), wherein X is the corresponding acid anion; reacting the Compound of formula (IV) with Ltartaric acid and a tertiary amine, to form the corresponding Compound of formula (V); suspending the Compound of formula (V) in an organic solvent, and treating with a Compound of formula (VI), (Rl0CO) 20, or a Compound of formula (VII), R1OC (0) Y, wherein Y is chlorine or bromine and wherein R1 is as set forth above, in the presence of a base, to form the corresponding Compound of formula (I). |
| 2. | A process for producing a compound of formula (I), wherein R1 and R2 are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, substituted aryl and aralkyl; comprising reacting () 2azabicyclo [2.2.1] hept5en3one of formula (II) with a compound of formula (III), an alcohol represented by the formula RlOH, wherein R1 is as described above, and a nonaqueous acid, to form the corresponding Compound of formula (IV), wherein X is the corresponding acid anion; reacting the compound of formula (IV) with Dtartaric acid and a tertiary amine, to form the corresponding compound of formula (VIII); collecting the compound of formula (VIII) by filtration; treating the filtrate containing the compound of formula (IVa) with Ltartaric acid and a tertiary amine, to form the corresponding compound of formula (V); suspending the Compound of formula (V) in an organic solvent, and treating with a Compound of formula (VI), (RlOCO) 20, or a Compound of formula (VII), R1OC (O) Y, wherein Y is chlorine or bromine and wherein Ru ils as set forth above, in the presence of a base, to form the corresponding Compound of formula (I). |
| 3. | The process of Claim 1, wherein R1 is tertbutyl and R2 is methyl. |
| 4. | The process of Claim 2, wherein Ru ils tertbutyl and R2 is methyl. |
| 5. | The process of Claim 3, wherein the nonaqueous acid is gaseous hydrochloric. |
| 6. | The process of Claim 4, wherein the nonaqueous acid is gaseous hydrochloric. |
| 7. | The process of Claim 3, wherein the Ltartaric acid is present in an amount in the range of 0.42.2eq. |
| 8. | The process of Claim 4, wherein the Dtartaric acid is present in an amount in the range of 0.42.2 eq. |
| 9. | The process of Claim 3, wherein the tertiary amine is triethylamine. |
| 10. | The process of Claim 4, wherein the tertiary amine is triethylamine. |
| 11. | The process of Claim 3, wherein when the compound of formula (IV) is treated with a tertiary amine, the tertiary amine is present in an amount sufficient to adjust the pH to between about 15. |
| 12. | The process of Claim 4, wherein when the compound of formula (IV) is treated with a tertiary amine, the tertiary amine is present in an amount sufficient to adjust the pH to between about 15. |
| 13. | The process of Claim 3, wherein when the compound of formula (V) is suspended in an organic solvent, the organic solvent is an alcohol of formula (III). |
| 14. | The process of Claim 4, wherein when the compound of formula (V) is suspended in an organic solvent, the organic solvent is an alcohol of formula (III). |
| 15. | The process of Claim 3, wherein when the compound of formula (V) is reacted in the presence of a base, the base is triethylamine, present in an amount equal to at least 2 equivalents. |
| 16. | The process of Claim 4, wherein when the compound of formula (V) is reacted in the presence of a base, the base is triethylamine, present in an amount equal to at least 2 equivalents. |
| 17. | A process for preparing a compound of formula (I) wherein P, and R2 are independently selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, substituted aryl and aralkyl; comprising reacting a Compound of formula (IV), wherein X is an acid anion of an acid and R2 is as set forth above, with Ltartaric acid and a tertiary amine, to form the corresponding Compound of formula (V); suspending the Compound of formula (V) in an alcohol of formula (III), R1OH, wherein Ru ils as set forth above, and treating with a Compound of formula (VI), (RlOCO) 2O, or a Compound of formula (VII), R10C (0) Y, wherein Y is chlorine or bromine and wherein R1 is as set forth above, in the presence of a tertiary amine, to form the corresponding Compound of formula (I). |
| 18. | A compound of formula (V) wherein R2 is selected from the group consisting of hydrogen, alkyl, cycloalkyl, aryl, substituted aryl and aralkyl. |
| 19. | A compound of formula (V) wherein R2 is methyl. |
Description:
INTERNATIONAL SEARCH REPORT International Application No.-2- PCT/US 00/15969 C. (Continuation) DOCUMENTS CONSIDERED TO BE RELEVANT Category Citation of document, with indication, where appropriate, of the relevant passages Relevant to ciaim No. abstract no. 175421u, TROST, B. M.:'An enantioselective syntheses of cis-4-tert-butoxycarbamoyl- -1-methoxycarbonyl-2- -cyclopentene-a useful, general building block' page 1230; column 1 ; &Chem.--Eur. J., vol. 1, no. 8,1995, pages 568-572, abstract. ANHAN-ANNEX ANNEXE Zum internationalen Recherchenbe-To the International Search Au rapport de recherche inter- richt uber die internationale Patent-Report to the international Patent national relativ à la demande de anmeldung Nr. Application No. brevet international n° PCT/US 00/15969 SAE 287597 In diesem Anhang sind die Mitglieder der This annex lists the patent family members La presente annexe indique les membres de Patentfamilien der im obengenannten relating to the patent documents cited in the la famille de brevets relatifs aux documents internationalen Recherchenbericht above-mentioned search report. de brevets cites dans le rapport de angefuhrten Patentdokumente angegeben. The European Patent Office is in no way recherche international visée ci-dessus. Les Diese Angaben dienen nur zur liable for these particulars which are merely renseignements fournis sont donnes à titre Unterrichtung und erfolgen ohne Gewahr. given for the purpose of information. indicatif et n'engagent pas la responsibilite de1'Office Im Recherchenbericht Datum der Mitglied (er) der Datum der angefuhrte Patentdokumente Veröffentlichung Patentfamilie Veröffentlichung Patent document cited Publication Patent family Publication in search report date member (s) date Document de brevet cite Date de Membre (s) de la Date de dans le rapport de recherche publication famille de brevets publication WOA2 9824741 11-06-1998 AU Al 55601/98 29-06-1998 WO A3 9824741 11-09-1998 EP A2 946496 06-10-1999 GB AO 9625455 22-01-1997 US A 6147254 14-11-2000 EP A1 590685 06-04-1994 DE CO 69302879 04-07-1996 EP B1 590685 29-05-1996 DE T2 69302879 23-01-1997 JP A2 6116217 26-04-1994 US A 5371282 06-12-1994 US A 5399580 21-03-1995 none