Method for producing 5-hydroxypiperidine-2-carboxylic acid

Patent metadata

Field	Value
Publication number	US-10370330-B2
Application number	US-201815965316-A
Country	US
Kind code	B2
Filing date	Apr 27, 2018
Priority date	Dec 27, 2013
Publication date	Aug 6, 2019
Grant date	Aug 6, 2019

Abstract

A method for producing (2S,5S)/(2R,5R)-5-hydroxypiperidine-2-carboxylic acid represented by the formula (10) below:

the method comprising the step of removing the protecting group from the hydroxyl group in a compound represented by the formula (7) below:

(wherein P represents a protecting group, R 3 represents an alkyl group containing 1 to 4 carbon atoms, and A represents an alkyl group containing 1 to 10 carbon atoms, an aryl group containing 6 to 12 carbon atoms, an alkyloxy group containing 1 to 4 carbon atoms, or an aralkyloxy group containing 7 to 20 carbon atoms) to synthesize a compound represented by the formula (8) below:

(wherein R 3 represents an alkyl group containing 1 to 4 carbon atoms, and A represents an alkyl group containing 1 to 10 carbon atoms, an aryl group containing 6 to 12 carbon atoms, an alkyloxy group containing 1 to 4 carbon atoms, or an aralkyloxy group containing 7 to 20 carbon atoms).

First claim

The invention claimed is:

1. A method for producing (2S,5S)/(2R,5R)-5-hydroxypiperidine-2-carboxylic acid represented by the formula (10) below:

the method comprising (i) the step of:
(a) hydrolyzing the ester groups of the compound (8) below:

wherein R 3 represents an alkyl group containing 1 to 4 carbon atoms, and A represents an alkyl group containing 1 to 10 carbon atoms, an aryl group containing 6 to 12 carbon atoms, an alkyloxy group containing 1 to 4 carbon atoms, or an aralkyloxy group containing 7 to 20 carbon atoms,
and allowing one of the carboxyl groups to react with the hydroxyl group to allow the lactonization, and further decarboxylating the other carboxyl group; or
(b) hydrolyzing the ester groups of the compound (8), decarboxylating one of the carboxyl groups to form a stereoisomeric mixture of a 2-monocarboxylic acid, and then isomerizing and lactonizing the stereoisomeric mixture;
to synthesize a compound represented by the formula (9) below:

wherein A represents an alkyl group containing 1 to 10 carbon atoms, an aryl group containing 6 to 12 carbon atoms, an alkyloxy group containing 1 to 4 carbon atoms, or an aralkyloxy group containing 7 to 20 carbon atoms.

2. The method for producing (2S,5S)/(2R,5R)-5-hydroxypiperidine-2-carboxylic acid according to claim 1 , further comprising (ii) the step of:
cleaving the amide bond in the compound (9) and hydrolyzing the lactone in the compound (9) to synthesize (2S,5S)/(2R,5R)-5-hydroxypiperidine-2-carboxylic acid.

Assignees

• Api Corp

Inventors

• Takehara Jun
• Murai Masato
• Ohtani Takashi
• Maeda Tomoko
• Hidaka Tsugihiko

Classifications

• Y02P20/55

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

• C07D498/08

  Bridged systems · CPC title

• C07C309/66

  Methanesulfonates · CPC title

• C07C233/47

  having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of an acyclic saturated carbon skeleton · CPC title

• C07D211/60 Primary

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