Benzocaine → 4-{2-[2-(4-Chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-2-cyclohexyl-acetylamino}-benzoic acid ethyl ester

Participants

Reaction Conditions

Reaction Steps

The solution of 3.0 g (7.4 mmol) [2-(4-chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-cyclohexyl-acetic acid in 5.4 ml thionylchloride was stirred under reflux. After 1 h the volatile components were removed at a rotary evaporator, the residue taken up in toluene and evaporated (three times). The remaining oil was dissolved in 30 ml dichloromethane, cooled to 0° C. and added dropwise on a solution of ethyl 4-aminobenzoate (1.35 g, 8.1 mmol) and 2.72 g (22.2 mmol) 4-dimethylaminopyridine dissolved in 30 ml dichloromethane. The cooling bath was removed and stirring was continued for another 4 h. The reaction was poured on 25% aqueous hydrochloric acid solution, the phases separated and the aqueous phase extracted with dichloromethane. The combined organic phases were washed with brine, dried over magnesium sulfate, filtered and evaporated. The residue was purified by column chromatography on silica gel using heptane:ethyl acetate (1:0 to 1:1 v/v) as eluant to afford the title compound as a colorless solid (2.6 g, 62%).

Provenance & Evidence