Thionyl Chloride → 3-Bromo-5-chloro-N-cyclopropyl-4-methylbenzamide

Participants

Reaction Conditions

Reaction Steps

3-Bromo-5-chloro-4-methylbenzoic acid (Intermediate 17, 310 mg, contaminated with 3-bromo-5-chloro-4-methylbenzoic acid) was mixed with thionyl chloride (3 ml) and the mixture heated at 90° C. for 2.5 hours. The excess thionyl chloride was evaporated under vacuum and the residue was dissolved in DCM (7.5 ml). Cyclopropylamine (0.2 ml) and sodium carbonate (500 mg) were added to the solution and the reaction stirred for 2 hours at room temperature. The reaction was filtered, the filtrate absorbed onto silica and applied to a SPE (Si, 10 g). The SPE was eluted with an ethyl acetate/cyclohexane gradient (p50% ethyl acetate) and the product fractions reduced to dryness under vacuum to give a mixture of 3-bromo-5-chloro-N-cyclopropyl-4-methylbenzamide/3-chloro-N-cyclopropyl-4-methylbenzamide (2:1).

Provenance & Evidence