Thionyl Chloride → N-[4-(Phenylsulfonyl)phenyl]-3,3-difluoro-2-hydroxy-2-difluoromethyl propionamide

Participants

Reaction Conditions

Reaction Steps

To a solution of 2,2-bis-difluoromethyl-2-hydroxyacetic acid (0.5 g, 2.84 mmoles) in dimethylacetamide (10 ml) at -10° C. was added thionyl chloride (0.34 g, 2.84 mmoles) dropwise. The resulting solution was stirred at -10° C. for approximately 30 mins. 4-(Phenylsulfonyl) aniline (0.58 g, 2.5 mmoles) was added and the reaction mixture was stirred overnight at room temperature. The reaction mixture was then poured into water, sodium bicarbonate solution added to give a pH of 7 and extracted with ethyl acetate. The ethyl acetate extracts were combined, washed with water, brine, dried (Na2SO4), decolorized (charcoal), and evaporated. The crude solid was dissolved in ether, clarified by filtration, and evaporated. Crystallization from methanol/water gave the title compound (0.56 g, 57%) as white, silky needles; mp 105°-108° C. 1H-NMR (300 MHz, d6 -DMSO) 6.44 (t, J=53.94 Hz, 2H, HCF2), 7.58-7.68(m, 3H, ArH), 7.92-8.01 (m, 7H, ArH, OH), 10.51 (s, 1H, NH). MS(CI,CH4): 392 (M+1, 100%). Analysis for C16H13F4NO4S: Calculated: C, 49.11; H, 3.35; N, 3.58. Found: C, 49.15; H, 3.48; N, 3.54

Provenance & Evidence