公开(公告)号：US20240002340A1

公开(公告)日：2024-01-04

申请号：US18243409

申请日：2023-09-07

Applicant: API CORPORATION

Inventor： Masato MURAI ,  Jun TAKEHARA ,  Daiki OKADO

IPC: C07D211/60

CPC classification number: 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：US20180244620A1

公开(公告)日：2018-08-30

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

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 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：US20180244619A1

公开(公告)日：2018-08-30

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：US20240150292A1

公开(公告)日：2024-05-09

申请号：US18390624

申请日：2023-12-20

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：US20210403427A1

公开(公告)日：2021-12-30

申请号：US17277456

申请日：2019-09-24

Applicant: API CORPORATION

Inventor： Masato MURAI ,  Jun TAKEHARA ,  Daiki OKADO

IPC: 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：US20160318867A1

公开(公告)日：2016-11-03

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: C07D211/60 ,  C07D498/08

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).

Abstract translation: （其中R3表示含有1至4个碳原子的烷基，A表示含有1至10个碳原子的烷基，含有6至12个碳原子的芳基，含有1至4个碳原子的烷氧基或芳烷氧基 含有7〜20个碳原子的基团）。

公开(公告)号：US20230192596A1

公开(公告)日：2023-06-22

申请号：US17999152

申请日：2021-05-14

Applicant: API CORPORATION

Inventor： Masato MURAI ,  Hirotsugu TANIIKE ,  Yurie KOBA

IPC: C07C231/10 ,  B01J23/44 ,  B01J31/06 ,  B01J35/02 ,  B01J35/10 ,  B01J35/00

CPC classification number: C07C231/10 ,  B01J23/44 ,  B01J31/06 ,  B01J35/026 ,  B01J35/1038 ,  B01J35/1042 ,  B01J35/1047 ,  B01J35/1019 ,  B01J35/1023 ,  B01J35/1028 ,  B01J35/1061 ,  B01J35/0066

Abstract: A method for producing acetaminophen may include causing p-nitrophenol to undergo an acetamination reaction to produce the acetaminophen, by passing a solution containing the p-nitrophenol through a column packed with a catalyst while also passing an acetylating agent and hydrogen through the column. The catalyst may be a supported metal catalyst in which a metal element is supported on a synthetic adsorbent, and a reaction temperature of the acetamination reaction is 0° C. to 60° C., and a reaction pressure of the acetamination reaction is 0.1 MPa to 1 MPa. With the method, it is possible to continuously produce acetaminophen safely and inexpensively with high selectivity and good yield, at a low reaction temperature and a low reaction pressure.

公开(公告)号：US20180002286A1

公开(公告)日：2018-01-04

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

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).