Method for preparing an optically pure benzofuran carboxylic acid and use thereof for preparing efaroxan

• US 5,880,296 A
• Filed: 11/10/1997
• Issued: 03/09/1999
• Est. Priority Date: 05/10/1995
• Status: Expired due to Fees

• Current Assignee: Pierre Fabre Medicament (Fondation Pierre Fabre)
• Original Assignee: Pierre Fabre Medicament (Fondation Pierre Fabre)
• Inventors: Imbert, Thierry, Mayer, Patrice
• Primary Examiner(s): DENTZ, BERNARD I
• Application Number:
  US08/952,133
• Time in Patent Office: 484 Days
• Field of Search: 549/468, 548/311.4
• US Class Current: 549/468
• CPC Class Codes: C07D 307/85 attached in position 2
• CPC Class Codes: C07D 405/04 directly linked by a ring-member-to-ring-member bond

Abstract

A method for preparing an optically pure 2-ethyl-2,3-dihydrobenzofurancarboxylic acid of formula II wherein R is a hydrogen atom, halogen, lower alkyl, lower alkoxy or hydroxy is described. ##STR1## The method comprises separating the racemic mixture by selective crystallization with the suitable optically pure enantiomer of 2-phenylglycinol, in a suitable solvent, whereafter the optically pure, crystallized acid of formula II is isolated and recovered. The invention also provides the optically pure 2-ethyl-2,3-dihydro-benzofurancarboxylic acid derivative thus obtained and the use thereof for the preparation of an optically pure derivative of efaroxan.

Claims

1. Process for the preparation of an optically pure 2-ethyl-2,3-dihydrobenzofurancarboxylic acid derivative of formula II ##STR7## in which R represents a hydrogen or halogen atom or a lower alkyl, lower alkoxy or hydroxyl radical, in which process the racemic mixture is resolved by selective crystallization with the appropriate optically pure enantiomer of 2-phenylglycinol, in a suitable solvent, after which the crystallized optically pure acid of formula II is recovered.

2. Process according to claim 1, wherein the acid of formula II of R-(+) configuration is obtained by selective crystallization with S-(+)-2-phenylglycinol.

3. Process according to claim 1 wherein the solvent is selected from acetone, ethyl acetate, methyl ethyl ketone and mixtures thereof.

4. Optically pure 2-ethyl-2,3-dihydrobenzofurancarboxylic acid of formula II which can be obtained by the process according to claim 1.

7. Process for the preparation of an optically pure 2- 2-(2-ethyl-2,3-dihydrobenzofuryl)!-2-imidazoline derivative of formula I ##STR9## in which R represents a hydrogen or halogen atom or a lower alkyl, lower alkoxy or hydroxyl radical, by conversion of the optically pure 2-ethyl-2,3-dihydrobenzofurancarboxylic acid derivative of corresponding formula II, defined according to one of claim 4.

8. Process according to claim 7, characterized in that the 2- 2-(2-ethyl-2,3-dihydrobenzofuryl)!-2-imidazoline derivative of formula I and the corresponding optically pure 2-ethyl-2,3-dihydrobenzofurancarboxylic acid of formula II are each of R configuration.

9. Process according to claim 8, characterized in that R represents a hydrogen atom and the 2- 2-(2-ethyl-2,3-dihydrobenzofuryl)!-2-imidazoline derivative of formula I and the corresponding optically pure 2-ethyl-2,3-dihydrobenzofurancarboxylic acid of formula II are each of R configuration and dextrorotatory (+).

5. Optically pure 2-ethyl-2,3-dihydrobenzofurancarboxylic acid of formula II, ##STR8##

6. Optically pure R-(+)-2-ethyl-2,3-dihydrobenzofurancarboxylic acid according to either of claim 5.