公开(公告)号：US10662145B2

公开(公告)日：2020-05-26

申请号：US16288031

申请日：2019-02-27

Applicant: FUDAN UNIVERSITY

Inventor： Fener Chen ,  Lingdong Wang ,  Ge Meng ,  Zedu Huang ,  Dang Cheng ,  Haihui Peng ,  Guanfeng Liang

IPC: C07C227/18 ,  C07C201/08 ,  C07C227/16 ,  C07C227/06

Abstract: The invention relates to the chemical synthesis of pharmaceutical API, and specifically to a method of synthesizing diclofenac sodium, which is a kind of nonsteroidal anti-inflammatory drug for relieving pain. The method includes: nitrating phenylacetate to prepare o-nitrophenylacetate (2); hydrogenating o-nitrophenylacetate (2) to prepare o-aminophenylacetate (3); amidating an amino group of o-aminophenylacetate (3) to obtain 2-(2-benzoylaminophenyl) acetate (4); 2-(2-benzoylaminophenyl) acetate (4) reacting with thionyl chloride to prepare a chloroimine intermediate, and then condensing the intermediate of chloroimine with 2,6-dichlorophenol using an inorganic base to prepare (E)-methyl-2-(2-((2,6-dichlorophenoxy)(phenyl)methyleneamino) phenyl ester (5); subjecting (E)-methyl-2-(2-((2,6-dichlorophenoxy)(phenyl)methyleneamino) phenyl ester (5) to Chapman rearrangement to afford methyl 2-(2-(N-(2,6-dichlorophenyl)benzoylamino)phenyl) ester (6); and hydrolyzing methyl 2-(2-(N-(2,6-dichlorophenyl)benzoylamino)phenyl) ester (6) to provide the target compound as of diclofenac sodium API. The overall yield is up to 67% based on methyl phenylacetate.

公开(公告)号：US10526622B2

公开(公告)日：2020-01-07

申请号：US15871039

申请日：2018-01-14

Applicant: FUDAN UNIVERSITY

Inventor： Fener Chen ,  Zedu Huang ,  Ge Meng ,  Minjie Liu ,  Zhining Li ,  Zexu Wang ,  Haihui Peng ,  Fangjun Xiong ,  Yan Wu ,  Yuan Tao

IPC: C12P7/62 ,  C07C69/732 ,  C12N9/04 ,  C07C67/28 ,  G01N30/02

Abstract: The present disclosure relates to the technical field of biochemical engineering and particularly discloses a preparation method for (R)-3-hydroxyl-5-hexenoate. In the method of the present disclosure, the (R)-3-hydroxyl-5-hexenoate is prepared by catalytic reduction of 3-carbonyl-5-hexenoate by ketoreductase with 3-carbonyl-5-hexenoate as the substrate. The amino acid sequence of ketoreductase is shown in SEQ ID NO.1. In the present disclosure, the (R)-3-hydroxyl-5-hexenoate having a very high chiral purity is obtained by asymmetric reduction by ketoreductase as the biocatalyst. The present disclosure has the advantages of easy operation, mild reaction conditions, high reaction yield and good practical industrial application value.

公开(公告)号：US10316012B1

公开(公告)日：2019-06-11

申请号：US16246531

申请日：2019-01-13

Applicant: FUDAN UNIVERSITY

Inventor： Fener Chen ,  Haihui Peng ,  Sha Hu ,  Ge Meng ,  Yan Wu ,  Dang Cheng ,  Zedu Huang ,  Guanfeng Liang

IPC: C07D307/93

Abstract: Disclosed is a method of synthesizing a series of compounds with the structure of (1S, 5R)-lactone. In the method, under the catalysis of a chiral phosphonic acid, substituted bicyclo[3.2.0]-hept-2-en-6-one (II) as a substrate is reacted with hydrogen peroxide for enantioselective Baeyer-Villiger oxidation to produce a chiral lactone (I). This method involves mild reaction conditions, simple operation, quantitatively recyclable catalyst and high reaction selectivity and stereoselectivity, which is suitable for industrial production.

公开(公告)号：US10214506B2

公开(公告)日：2019-02-26

申请号：US15871049

申请日：2018-01-14

Applicant: FUDAN UNIVERSITY

Inventor： Fener Chen ,  Guanxin Huang ,  Ge Meng ,  Minjie Liu ,  Yan Wu ,  Dang Cheng ,  Zedu Huang ,  Haihui Peng ,  Fangjun Xiong

IPC: C07D319/06 ,  C07B47/00 ,  C07B41/12

Abstract: The present disclosure belongs to the technical field of organic synthesis and particularly relates to a preparation method for 2-((4R,6S)-6-bromomethyl-2-oxo-1,3-dioxane-4-yl)acetate. The 2-((4R,6S)-6-bromomethyl-2-oxo-1,3-dioxane-4-yl)acetate is a key chiral intermediate for preparation of statin antilipemic agents. In the present disclosure, the 2-((4R,6S)-6-bromomethyl-2-oxo-1,3-dioxane-4-yl)acetate is obtained by bromination and cyclization of 3-((substituted oxycarbonyl)oxy)-5-hexenoate as raw material with hypochlorite and bromide in an organic solvent in the presence of CO2. The method of the present disclosure has the advantages of readily available raw material, mild reaction conditions, easy operation, low cost, excellent atomic economy and less by-products, and is applicable to industrial production.