Method for producing 5-hydroxypiperidine-2-carboxylic acid

Patent metadata

Field	Value
Publication number	US-9988351-B2
Application number	US-201715705349-A
Country	US
Kind code	B2
Filing date	Sep 15, 2017
Priority date	Dec 27, 2013
Publication date	Jun 5, 2018
Grant date	Jun 5, 2018

Abstract

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

the method including removing the protecting group from the hydroxyl group in a compound represented by 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 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 a compound represented by formula (9),

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, the method comprising
(i) removing the ether protecting group from the hydroxyl group in the compound represented by formula (7) below:

wherein P represents an ether protecting group that is resistant to basic reaction conditions, 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 the compound represented by 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;
and
(ii) (a) in the compound (8), hydrolyzing the ester groups, 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) in the compound (8), hydrolyzing the ester groups, 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 the 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. A compound represented by formula (9a) below:

wherein A′ represents an alkyl group containing 1 to 10 carbon atoms or an aryl group containing 6 to 12 carbon atoms.

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

• 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

• C07C309/66

  Methanesulfonates · CPC title

• C07D498/08

  Bridged systems · 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