Development and a practical synthesis of nepafenac intermediate via modified gassman reaction

Article abstract of DOI:10.2174/157017812802139582

Modification of nepafenac intermediate synthesis (5A) via Gassman specific ortho-substitution is reported. According to the process, 2-aminobenzophenone (1A) and 2-(methylthio)acetamide (2) were reacted in the convenient temperature conditions, in the presence of N-chlorophthalimide (3) or 1,3-dichloro-5,5- dimethylhydantoin (4), to activate the formation of azasulfonium salt and rearrangement thereof to pure 2-amino-3-benzoyl-α-(methylthio) phenylacetamide (5A). The procedure appears to be suitable for a reaction carried out in a large scale.