公开(公告)号：US20230234911A1

公开(公告)日：2023-07-27

申请号：US18172414

申请日：2023-02-22

Applicant: Fudan University

Inventor： Fener CHEN ,  Dang CHENG ,  Lulu WANG ,  Ge MENG ,  Yingtang NING ,  Zedu HUANG

IPC: C07C227/18 ,  B01J21/02

CPC classification number: C07C227/18 ,  B01J21/02

Abstract: A method of synthesizing diclofenac sodium, including: subjecting aniline and chloroacetic acid to amidation to obtain 2-chloro-N-phenylacetamide; subjecting 2-chloro-N-phenylacetamide and 2,6-dichlorophenol to condensation reaction to obtain 2-(2,6-dichlorophenoxy)-N-phenylacetamide; subjecting 2-(2,6-dichlorophenoxy)-N-phenylacetamide to Smiles rearrangement in the presence of an inorganic base to obtain N-(2,6-dichlorophenyl)-2-hydroxy-N-phenylacetamide; subjecting N-(2,6-dichlorophenyl)-2-hydroxy-N-phenylacetamide and thionyl chloride to chlorination to obtain N-(2,6-dichlorophenyl)-2-chloro-N-phenylacetamide; subjecting N-(2,6-dichlorophenyl)-2-chloro-N-phenylacetamide to Friedel-Crafts alkylation in the presence of a Lewis acid catalyst to obtain 1-(2,6-dichlorophenyl)-1,3-dihydro-2H-indol-2-one; and subjecting 1-(2,6-dichlorophenyl)-1,3-dihydro-2H-indol-2-one to hydrolysis in the presence of an inorganic base to obtain diclofenac sodium.

公开(公告)号：US20230192595A1

公开(公告)日：2023-06-22

申请号：US18172865

申请日：2023-02-22

Applicant: Fudan University

Inventor： Fener CHEN ,  Dang CHENG ,  Lulu WANG ,  Ge MENG ,  Yingtang NING

IPC: C07C227/18 ,  C07C227/40

CPC classification number: C07C227/18 ,  C07C227/40

Abstract: This application relates to pharmaceutical engineering, and more particularly to a continuous-flow preparation method of diclofenac sodium. The continuous-flow preparation method includes: subjecting aniline and chloroacetic acid to amidation to obtain 2-chloro-N-phenylacetamide (3); subjecting 2-chloro-N-phenylacetamide (3) and 2,6-dichlorophenol to continuous condensation to obtain N-(2,6-dichlorophenyl)-2-hydroxy-N-phenylacetamide (5); subjecting N-(2,6-dichlorophenyl)-2-hydroxy-N-phenylacetamide (5) and thionyl chloride to chlorination to obtain N-(2,6-dichlorophenyl)-2-chloro-N-phenylacetamide (6); subjecting N-(2,6-dichlorophenyl)-2-chloro-N-phenylacetamide (6) to Friedel-Crafts alkylation in the presence of aluminum chloride to obtain 1-(2,6-dichlorophenyl)-1,3-dihydro-2H-indo1-2-one (7); and subjecting 1-(2,6-dichlorophenyl)-1,3-dihydro-2H-indol-2-one (7) to hydrolysis to obtain the diclofenac sodium.