Thionyl Chloride → N-[4-(N,N-Dimethylaminosulfonyl)phenyl]-3,3,3-trifluoro-2-hydroxy-2-methylpropanamide

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Reaction Conditions

Reaction Steps

To a cooled (-10° C.) solution of α-trifluoromethyl lactic acid (0.69 g) in dry N,N-dimethylacetamide (5 ml) was added thionyl chloride (0.33 ml) dropwise over 2 minutes. The mixture was stirred at -10° C. for 90 minutes, then treated successively with 4-pyrrolidinopyridine (13 mg), di-isopropylethylamine (0.76 ml), and 4-(N,N-dimethylaminosulfonyl)aniline (0.88 g). The reaction mixture was stirred at 22° C. for 48 hours, then diluted with water and extracted with ethyl acetate. The combined ethyl acetate extracts were washed with 1N HCl, brine, dried and the solvent evaporated. The crude product was purified by chromatography (12:1 CH2Cl2 : ethyl acetate) and recrystallised from methyl-t-butyl ether/hexane to give the title compound as a colourless crystalline solid (0.56 g); mp 139°-141° C.; MS: m/z=341(M+1); NMR (250 MHz): 1.60 (s,3), 2.58 (s,6), 7.58 (s,1), 7.69-7.73 (d,2), 8.03-8.06 (d,2). Analysis for C12H15F3N2O4S: Calculated: C, 42.35; H, 4.44; N, 8.23; Found: C, 42.21; H, 4.54; N, 8.15.

Provenance & Evidence