Method for improving optical purity of 2-hydroxycarboxylic acid or derivative thereof

Patent metadata

Field	Value
Publication number	US-9682913-B2
Application number	US-201414780625-A
Country	US
Kind code	B2
Filing date	Mar 28, 2014
Priority date	Mar 29, 2013
Publication date	Jun 20, 2017
Grant date	Jun 20, 2017

Abstract

To provide a method for improving optical purity of an optically active 2-hydroxycarboxylic acid or a derivative thereof, which is useful as a raw material in the manufacture of medicines, agrochemicais, and industrial products. The method of the invention for improving purity of a hydroxycarboxylic acid of the following formula (1a) or (1b) or a derivative thereof includes the steps of reacting the hydroxycarboxylic acid of the following formula (1a) or (1b) with at least one optically inactive base selected from the group consisting of an alkali metal, alkoxide and a secondary amine in the presence of a solvent and, subsequently, performing recrystallization, to thereby form a hydroxycarboxylic acid salt of the following formula (IIIa) or (IIIb):

wherein R 1 represents a C 1-8 alkyl group, and R 2 represents an alkali metal or a secondary amine.

First claim

The invention claimed is:

1. A method for improving optical purity of a hydroxycarboxylic acid of the following formula (1a) or (1b) or a derivative thereof, the method comprising the steps of:
reacting the hydroxycarboxylic acid of the following formula (1a) or (1b):

wherein R 1 represents a C 1-8 alkyl group, with at least one optically inactive base selected from the group consisting of an alkali metal alkoxide and a secondary amine in the presence of a solvent and, subsequently,
performing recrystallization, to thereby form a hydroxycarboxylic acid salt of the following formula (IIIa) or (IIIb):

wherein R 1 has the same meaning as defined above, and R 2 represents an alkali metal or a secondary amine.

2. A method for improving optical purity of a hydroxycarboxylic acid of the following formula (1a) or (1 b) or a derivative thereof, the method comprising a first step of:
reacting the hydroxycarboxylic acid of the following formula (1a) or (1 b):

wherein R 1 represents a C 1-8 alkyl group, with at least one optically inactive base selected from the group consisting of an alkali metal alkoxide and a secondary amine in the presence of a solvent and, subsequently, performing recrystallization, to thereby form a hydroxycarboxylic acid salt of the following formula (IIIa) or (IIIb):

wherein R 1 has the same meaning as defined above, and R 2 represents an alkali metal or a secondary amine, and a second step of:
reading the hydroxycarboxylic acid salt with an organic acid or an inorganic acid, to thereby form the hydroxycarboxylic acid of formula (1a) or (1b).

3. A method for improving optical purity of a hydroxycarboxylic acid of the following formula (1a) or (1 b) or a derivative thereof, the method comprising a first step of:
reacting the hydroxycarboxylic acid of the following formula (1a) or (1 b):

wherein R 1 represents a C 1-8 alkyl group, with at least one optically inactive base selected from the group consisting of an alkali metal alkoxide and a secondary amine in the presence of a solvent and, subsequently, performing recrystallization, to thereby form a hydroxycarboxylic acid salt of the following formula (IIIa) or (IIIb):

wherein R 1 has the same meaning as defined above, and R 2 represents an alkali metal or a secondary amine,
a second step of reacting the hydroxycarboxylic acid salt with an organic acid or an inorganic acid to thereby obtain a hydroxycarboxylic acid of the following formula (1a) or (1b), and
a step of esterifying the hydroxycarboxylic acid formed in the second step.

4. A method for improving optical purity of a hydroxycarboxylic acid of the following formula (1a) or (1 b) or a derivative thereof, the method comprising the steps of:
reacting the hydroxycarboxylic acid of the following formula (1a) or (1 b):

wherein R 1 represents a C 1-8 alkyl group, with at least one optically inactive base selected from the group consisting of alkali metal alkoxide and secondary amine in the presence of a solvent and, subsequently, performing recrystallization, to thereby form a hydroxycarboxylic acid salt of the following formula (IIIa) or (IIIb):

wherein R 1 has the same meaning as defined above, and R 2 represents an alkali metal or a secondary amine, and esterifying the hydroxycarboxylic acid salt.

5. A method according to any one of claims 1 to 4 , wherein R 1 is an ethyl group.

6. A method according to any one of claims 1 to 4 , wherein the optically inactive base is a sodium alkoxide.

7. A method according to claim 6 , wherein the sodium alkoxide is sodium methoxide.

8. A method according to any one of claims 1 to 4 , wherein the optically inactive base is dicyclohexylamine.

9. A method according to any one of claims 1 to 4 , wherein recrystallization is performed using a solvent containing at least one member selected from the group consisting of an ester, an ether, and an alcohol.

Assignees

• Kowa Co

Inventors

• Yamazaki Yukiyoshi

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P3/06

  Antihyperlipidemics · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61K31/423 Primary

  condensed with carbocyclic rings · CPC title