公开(公告)号：US10703719B2

公开(公告)日：2020-07-07

申请号：US15965289

申请日：2018-04-27

Applicant: API CORPORATION

Inventor： Jun Takehara ,  Masato Murai ,  Takashi Ohtani ,  Tomoko Maeda ,  Tsugihiko Hidaka

IPC: C07D211/60 ,  C07C309/66 ,  C07C233/47 ,  C07D498/08

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, R3 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 R3 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).

公开(公告)号：US09988351B2

公开(公告)日：2018-06-05

申请号：US15705349

申请日：2017-09-15

Applicant: API CORPORATION

Inventor： Jun Takehara ,  Masato Murai ,  Takashi Ohtani ,  Tomoko Maeda ,  Tsugihiko Hidaka

IPC: C07D498/08 ,  C07C233/47 ,  C07C309/66 ,  C07D211/60

CPC classification number: C07D211/60 ,  C07C233/47 ,  C07C309/66 ,  C07D498/08 ,  Y02P20/55

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, R3 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 R3 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).

公开(公告)号：US12202800B2

公开(公告)日：2025-01-21

申请号：US18243409

申请日：2023-09-07

Applicant: API CORPORATION

Inventor： Masato Murai ,  Jun Takehara ,  Daiki Okado

IPC: C07D211/60

Abstract: A method for producing a compound represented by the formula (1): wherein LG is a leaving group, PG1 is an amino-protecting group, and R is a hydrocarbon group having 1-8 carbon atoms and optionally having substituent(s), comprising reacting a compound represented by the formula (6): with an amino group protecting agent to obtain a compound represented by the formula (7): or a salt thereof; reacting the aforementioned compound represented by the formula (7) with a lactonization agent to obtain a compound represented by the formula (8): reacting the aforementioned compound represented by the formula (8) with an esterification agent to obtain a compound represented by the formula (9): and reacting the aforementioned compound represented by the formula (9) with a leaving group introduction agent.

公开(公告)号：US09790181B2

公开(公告)日：2017-10-17

申请号：US15108141

申请日：2014-12-26

Applicant: API CORPORATION

Inventor： Jun Takehara ,  Masato Murai ,  Takashi Ohtani ,  Tomoko Maeda ,  Tsugihiko Hidaka

IPC: C07D211/16 ,  C07D498/08 ,  C07D211/60 ,  C07C309/66 ,  C07C233/47

CPC classification number: C07D211/60 ,  C07C233/47 ,  C07C309/66 ,  C07D498/08 ,  Y02P20/55

Abstract: A method for producing (2S,5S)/(2R,5R)-5-hydroxypiperidine-2-carboxylic acid represented by 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, R3 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 R3 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).

公开(公告)号：US20150239906A1

公开(公告)日：2015-08-27

申请号：US14431141

申请日：2013-12-19

Applicant: API CORPORATION

Inventor： Tomoko Maeda ,  Hisatoshi Uehara ,  Yasuyo Saito ,  Masato Murai

IPC: C07D498/08 ,  C07D211/60

CPC classification number: C07D498/08 ,  C07D211/60 ,  C12P17/12 ,  Y02P20/55

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 R1 represents a protective group for an amino group, and R2 represents a C1-C6 alkyl group), and a method for purifying cis-5-hydroxy-2-piperidinecarboxylic acid.

Abstract translation: 本发明旨在提供一种纯度高的顺式-5-羟基-2-哌啶羧酸的纯化方法及其衍生物的制造方法。 本发明提供了顺式-5-羟基-2-哌啶羧酸衍生物的制备方法，该方法包括将顺式-5-羟基-2-哌啶羧酸转化成式（1）的化合物和 /或式（2）（其中R1表示氨基的保护基，R2表示C1-C6烷基）和顺式-5-羟基-2-哌啶羧酸的纯化方法。

公开(公告)号：US11897844B2

公开(公告)日：2024-02-13

申请号：US17277456

申请日：2019-09-24

Applicant: API CORPORATION

Inventor： Masato Murai ,  Jun Takehara ,  Daiki Okado

IPC: C07D211/60

CPC classification number: C07D211/60

Abstract: The present invention aims to provide a method for producing a (2S,5R)-5-(protected oxyamino)-piperidine-2-carboxylic acid derivative at a low cost that can be performed under mild reaction conditions not requiring a facility at an extremely low temperature, is safer, can control the quality of the desired product with ease, and shows good workability in the site of production. A method for producing a compound represented by the formula (2):




wherein PG1 is an amino-protecting group, PG2 is an amino-protecting group, PG3 is a hydroxyl-protecting group, LG is a leaving group, and R is a hydrocarbon group having 1-8 carbon atoms and optionally having substituent(s), including a step of reacting a compound represented by the formula (1):





wherein each symbol is as defined above, with a hydroxylamine derivative represented by the formula PG2NHOPG3 wherein each symbol is as defined above, in the presence of a base in a solvent.

公开(公告)号：US10370330B2

公开(公告)日：2019-08-06

申请号：US15965316

申请日：2018-04-27

Applicant: API CORPORATION

Inventor： Jun Takehara ,  Masato Murai ,  Takashi Ohtani ,  Tomoko Maeda ,  Tsugihiko Hidaka

IPC: C07D211/60 ,  C07C309/66 ,  C07C233/47 ,  C07D498/08

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, R3 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 R3 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).

公开(公告)号：US09981984B2

公开(公告)日：2018-05-29

申请号：US14431141

申请日：2013-12-19

Applicant: API Corporation

Inventor： Tomoko Maeda ,  Hisatoshi Uehara ,  Yasuyo Saito ,  Masato Murai

IPC: C07D498/08 ,  C07D211/60 ,  C12P17/12

CPC classification number: C07D498/08 ,  C07D211/60 ,  C12P17/12 ,  Y02P20/55

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 R1 represents a protective group for an amino group, and R2 represents a C1-C6 alkyl group), and a method for purifying cis-5-hydroxy-2-piperidinecarboxylic acid.