公开(公告)号：US20180370914A1

公开(公告)日：2018-12-27

申请号：US16062846

申请日：2017-04-25

申请人： Chen-Stone (Guangzhou) Co., Ltd.

发明人： Yingjie Lai ,  Dabing Ye ,  Fengrui Lang ,  Xiangtian Long

IPC分类号： C07D209/54

CPC分类号： C07D209/54 ,  Y02P20/55

摘要： The present invention discloses a preparation method for efficient synthesis of sitafloxacin intermediate (7S)-5-azaspiro[2.4]heptane-7-yl-tert-butyl carbamate, comprising the following steps: reacting to obtain reacting to obtain reacting to obtain and reacting to obtain In the present invention, a single compound with a relatively high ee value can be obtained, the unnecessary waste of materials is avoided, the yield is significantly improved, the operation is simple, the industrial scale-up is easy, and the production cost is reduced.

公开(公告)号：US10385000B2

公开(公告)日：2019-08-20

申请号：US16061880

申请日：2017-04-25

申请人： CHEN-STONE (GUANGZHOU) CO., LTD.

发明人： Yingjie Lai ,  Xuyan Wang

IPC分类号： C07C51/09 ,  C07C61/15 ,  C07C51/377 ,  C07C315/04 ,  C07C317/22

摘要： Disclosed is a new method for synthesizing 2-fluorocyclopropanecarboxylic acid comprising: 1) performing reaction of 1,1-dichloro-1-fluoroethane with thiophenol in the presence of an alkali, to produce a phenyl sulfide intermediate; 2) performing oxidation reaction of the phenyl sulfide intermediate with Oxone; 3) performing elimination reaction of the product of Step 2) in the presence of an alkali, to obtain 1-fluoro-1-benzenesulfonyl ethylene; 4) performing addition reaction of the 1-fluoro-benzenesulfonyl ethylene with ethyl diazoacetate in the presence of a catalyst, to obtain a cyclopropane intermediate; 5) performing elimination reaction of the cyclopropane intermediate in the presence of an alkali before acidification, to obtain 2-fluorocyclopropanecarboxylic acid. Herein, the synthetic route is short, used materials are bulk commodities, and raw materials are inexpensive and readily available. The process can be safely scaled up by replacing commonly used mCPBA reagents with Oxone. Further, reaction yield is improved, production cost is greatly reduced, and operation is simplified.

公开(公告)号：US10358417B2

公开(公告)日：2019-07-23

申请号：US16062846

申请日：2017-04-25

申请人： Chen-Stone (Guangzhou) Co., Ltd.

发明人： Yingjie Lai ,  Dabing Ye ,  Fengrui Lang ,  Xiangtian Long

IPC分类号： C07D209/54

摘要： The present invention discloses a preparation method for efficient synthesis of sitafloxacin intermediate (7S)-5-azaspiro[2.4]heptane-7-yl-tert-butyl carbamate, comprising the following steps: reacting to obtain reacting to obtain reacting to obtain and reacting to obtain In the present invention, a single compound with a relatively high ee value can be obtained, the unnecessary waste of materials is avoided, the yield is significantly improved, the operation is simple, the industrial scale-up is easy, and the production cost is reduced.

公开(公告)号：US20180370893A1

公开(公告)日：2018-12-27

申请号：US16061880

申请日：2017-04-25

申请人： CHEN-STONE (GUANGZHOU) CO., LTD.

发明人： Yingjie LAI ,  Xuyan WANG

IPC分类号： C07C51/09 ,  C07C61/15

CPC分类号： C07C51/09 ,  C07C51/377 ,  C07C61/15 ,  C07C315/04 ,  C07C317/22 ,  C07C317/44 ,  C07C317/14

摘要： Disclosed is a new method for synthesizing 2-fluorocyclopropanecarboxylic acid comprising: 1) performing reaction of 1,1-dichloro-1-fluoroethane with thiophenol in the presence of an alkali, to produce a phenyl sulfide intermediate; 2) performing oxidation reaction of the phenyl sulfide intermediate with Oxone; 3) performing elimination reaction of the product of Step 2) in the presence of an alkali, to obtain 1-fluoro-1-benzenesulfonyl ethylene; 4) performing addition reaction of the 1-fluoro-benzenesulfonyl ethylene with ethyl diazoacetate in the presence of a catalyst, to obtain a cyclopropane intermediate; 5) performing elimination reaction of the cyclopropane intermediate in the presence of an alkali before acidification, to obtain 2-fluorocyclopropanecarboxylic acid. Herein, the synthetic route is short, used materials are bulk commodities, and raw materials are inexpensive and readily available. The process can be safely scaled up by replacing commonly used mCPBA reagents with Oxone. Further, reaction yield is improved, production cost is greatly reduced, and operation is simplified.