Method for producing cis-5-hydroxy-2-piperidinecarboxylic acid derivative, and method for purifying cis-5-hydroxy-2-piperidinecarboxylic acid

Patent metadata

Field	Value
Publication number	US-9981984-B2
Application number	US-201314431141-A
Country	US
Kind code	B2
Filing date	Dec 19, 2013
Priority date	Dec 20, 2012
Publication date	May 29, 2018
Grant date	May 29, 2018

Abstract

The present invention aims to provide a method for purifying cis-5-hydroxy-2-piperidinecarboxylic acid with high purity, and a method for producing its derivative. The present invention provides a method for producing a cis-5-hydroxy-2-piperidinecarboxylic acid derivative, which method comprises a step of converting cis-5-hydroxy-2-piperidinecarboxylic acid into a compound(s) of Formula (1) and/or Formula (2) (wherein R 1 represents a protective group for an amino group, and R2 represents a C 1 -C 6 alkyl group), and a method for purifying cis-5-hydroxy-2-piperidinecarboxylic acid.

First claim

The invention claimed is:

1. A method for producing a compound of Formula (1), said method comprising a step of reacting a mixture containing cis-5-hydroxy-2-piperidinecarboxylic acid and an impurity with a single kind of an acid halide, an acid anhydride, an acid halide and an acid anhydride in a single reactor to convert said cis-5-hydroxy-2-piperidinecarboxylic acid into a compound of Formula (1) by protecting and lactonizing said cis-5-hydroxy-2-piperidinecarboxylic acid with the single kind of the acid halide, the acid anhydride, or the acid halide and the acid anhydride in the single reactor,
wherein R 1 represents a protective group for an amino group, and
wherein the impurity comprises trans-5-hydroxy-2-piperidinecarboxylic acid.

2. The method according to claim 1 , further comprising the step of synthesizing cis-5-hydroxy-2-piperidinecarboxylic acid by bacterial reaction and/or enzymatic reaction.

3. The method according to claim 1 , further comprising a step of separating the compound of Formula (1) by crystallization or solvent extraction.

4. The method according to claim 1 , wherein said impurity further comprises (2S,3S)-3-hydroxy-2-piperidinecarboxylic acid.

5. The method according to claim 1 , wherein a mixture containing cis-5-hydroxy-2-piperidinecarboxylic acid and an impurity is reacted with a single kind of an acid halide.

6. The method according to claim 5 , wherein said acid halide comprises benzyloxycarbonyl chloride.

7. The method according to claim 1 , wherein:
the single kind of the acid halide, the acid anhydride, or the acid halide and the acid anhydride comprises the R 1 protective group;
the single kind of the acid halide, the acid anhydride, or the acid halide and the acid anhydride protects the amino group with the R 1 protective group in the compound of Formula (1); and
the single kind of the acid halide, the acid anhydride, or the acid halide and the acid anhydride allows the lactonization of the cis-5-hydroxy-2-piperidinecarboxylic acid to convert the cis-5-hydroxy-2-piperidinecarboxylic acid into the compound of Formula (1).

8. The method according to claim 1 , further comprising a step of separating the compound of Formula (1) by solvent extraction.

Assignees

• Api Corp

Inventors

• Maeda Tomoko
• Uehara Hisatoshi
• Saito Yasuyo
• Murai Masato

Classifications

• C12P17/12

  containing a six-membered hetero ring · CPC title

• Y02P20/55

  Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups · CPC title

• C07D498/08 Primary

  Bridged systems · CPC title

• C07D211/60

  Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals · CPC title