US 11,905,229 B2
Method for synthesizing diclofenac sodium
Fener Chen, Shanghai (CN); Dang Cheng, Shanghai (CN); Lulu Wang, Shanghai (CN); Ge Meng, Shanghai (CN); Yingtang Ning, Shanghai (CN); and Zedu Huang, Shanghai (CN)
Assigned to Fudan University, Shanghai (CN)
Filed by Fudan University, Shanghai (CN)
Filed on Feb. 22, 2023, as Appl. No. 18/172,414.
Claims priority of application No. 202210178956.5 (CN), filed on Feb. 25, 2022.
Prior Publication US 2023/0234911 A1, Jul. 27, 2023
This patent is subject to a terminal disclaimer.
Int. Cl. C07C 227/18 (2006.01); B01J 21/02 (2006.01)
CPC C07C 227/18 (2013.01) [B01J 21/02 (2013.01)] 10 Claims
 
1. A method for synthesizing diclofenac sodium, comprising:
(S1) subjecting aniline and chloroacetic acid to amidation in an organic solvent in the presence of a boric acid catalyst to obtain 2-chloro-N-phenylacetamide (II);
(S2) subjecting 2-chloro-N-phenylacetamide (II) and 2,6-dichlorophenol to condensation reaction in the presence of potassium carbonate and a phase transfer catalyst to obtain 2-(2,6-dichlorophenoxy)-N-phenylacetamide (III);
(S3) subjecting 2-(2,6-dichlorophenoxy)-N-phenylacetamide (III) to Smiles rearrangement in the presence of a basic catalyst to obtain N-(2,6-dichlorophenyl)-2-hydroxy-N-phenylacetamide (IV);
(S4) subjecting N-(2,6-dichlorophenyl)-2-hydroxy-N-phenylacetamide (IV) and thionyl chloride to chlorination in the presence of a catalyst to obtain N-(2,6-dichlorophenyl)-2-chloro-N-phenylacetamide (V);
(S5) subjecting N-(2,6-dichlorophenyl)-2-chloro-N-phenylacetamide (V) 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 (VI); and
(S6) subjecting 1-(2,6-dichlorophenyl)-1,3-dihydro-2H-indol-2-one (VI) to hydrolysis in the presence of an inorganic base to obtain diclofenac sodium (I).