Methanesulfonamide → 5-Chloro-2-fluoro-4-methyl-N-(methylsulfonyl)benzamide

Participants

Reaction Steps

To a solution of 5-chloro-2-fluoro-4-methylbenzoic acid (Preparation 21, 200 g, 1.06 mol) in DCM (1.4 L) were added methanesulphonamide (152 g, 1.6 mol), 4-(dimethylamino)pyridine (183 g 1.6 mol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (306 g, 1.6 mol). An exotherm of 30° C. was observed in the first 30 minutes, then the mixture was stirred at room temperature for 18 hours under a nitrogen atmosphere. The reaction mixture was washed with aqueous hydrochloric acid (4 M, 0.8 L). The organic layer was separated, washed with water (500 mL) and dried over sodium sulfate to yield a tan solid, which was recrystallised from hot EtOAc (0.9 L) by addition of n-heptane (100 mL) and cooling to afford the title compound (118 g, 45%).

Provenance & Evidence