Process for preparing prostaglandin derivatives and starting materials for the same

• US 20050272943A1
• Filed: 09/18/2003
• Published: 12/08/2005
• Est. Priority Date: 09/18/2002
• Status: Active Grant

• Current Assignee: Yonsung Fine Chemical Co., Ltd.
• Original Assignee: Yonsung Fine Chemical Co., Ltd.
• Inventors: Lee, Yiu-Suk, Kim, Yong-Hyun
• Granted Patent: US 7,345,181 B2
• Time in Patent Office: Days
• US Class Current: 549/458
• CPC Class Codes: C07D 307/93 condensed with a ring other than six-membered
• CPC Class Codes: C07F 7/1892 by reactions not provided for in C07F7/1876 - C07F7/1888
• CPC Class Codes: C07F 7/2208 Compounds having tin linked only to carbon, hydrogen and/or halogen
• CPC Class Codes: Y02P 20/55 Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

Abstract

The present invention provides a process for preparing benzoprostacycline derivatives of formula (1), i.e. 5,6,7-trinor-4,8-inter-m-phenylene PGI2 derivatives, and vinyl tin compounds of formula (III) as starting materials for the same.

Claims

1. A process for preparing a compound of the following formula:

2. The process of claim 1, wherein R², R³, R^2a and R^3a each represent trimethylsilyl, triethylsilyl, t-butyldimethylsilyl, t-butyldiphenylsilyl, phenyldimethylsilyl, or tetrahydropyranyl, and R′

represents methyl, methoxymethyl, methoxyethyl, benzyloxymethyl, or p-benzyloxymethyl.

3. The process of claim 1, wherein in step (2) the reduction is performed with using a metal hydride.

4. The process of claim 3, wherein the metal hydride is selected from the group consisting of sodium borohydride (NaBH₄), L-selectride, N-selectride and K-selectride.

5. The process of claim 1, wherein in step (3), i) the α

-alcohol is converted into a leaving group, and then, the leaving group is converted into the β

-halide via SN₂ reaction with the halide nucleophile, or ii) the α

-alcohol is directly converted into the β

-halide using trialkylphosphine and carbon tetrahalide.

6. The process of claim 1, wherein in step (4) the hydroxy protective group is deprotected under an acidic condition.

7. The process of claim 1, wherein in step (5) the cyclization reaction is performed in the presence of base.

8. A compound of the following formula: