Process of preparing a 3-phenyl-4-(methylsulphonyl)-phenyl-furan-2-one derivative which is useful as COX-2 inhibitor

摘要

The method of preparing a 3-phenyl-4-(methylsulphonyl)-phenyl-furan-2-one derivative of formula I comprises: a) reacting a bromoketone of formula 2 with a phenyl acetic acid of formula 2a in N,N-dimethylformamide and in the presence of an inorganic base to yield a phenyl acetic ester of formula 5a and b) treating the phenyl acetic ester 5a with an organic base in polar aprotic solvent to yield the furan-2-one I. The inorganic base can be sodium hydroxide and the polar aprotic solvent can be N,N-dimethylformamide. The synthesis of the bromoketone of formula 2 is: c) reacting thioanisole with acetyl chloride in an inert solvent in the presence of aluminum chloride to yield a ketosulphide of formula 3; d) oxidizing the ketosulphide 3 with an oxidizing agent in an inert solvent in the presence of a phase transfer catalyst to yield a ketosulphone of formula 4 and e) reacting the ketosulphone 4 with bromine in an aqueous acetic acid to yield the bromoketone 2. In the above formulae: R2 is an optionally substituted phenyl and R3 and R3' are independently H or alkyl. An specific example of the above processes is depicted in scheme 1 depicted above.