Sulfoxonium, trimethyl-, iodide (1:1) → 4-((6-((2-(2,4-Difluorophenyl)oxiran-2-yl)difluoromethyl)pyridin-3-yl)oxy)benzonitrile

Participants

Reaction Steps

To a magnetically stirred solution of trimethylsulfoxonium iodide (6.4 g, 29.42 mmol) in dry THF/DMSO (10:6) was added potassium tert-butoxide (3.302 g, 29.42 mmol) under a N2 atmosphere. The reaction mixture was stirred at room temperature for 1 h and then cooled to 0° C. 4-((6-(2-(2,4-Difluorophenyl)-1,1-difluoro-2oxoethyl)pyridin-3-yl)oxy)benzonitrile (8.737 g, 22.63 mmol) in THF (40 mL) was added slowly to maintain the temperature below 5° C. The reaction mixture was maintained at 0° C. for 30 min and saturated sodium bicarbonate was added to quench the reaction. Brine was added and the mixture was extracted with Et2O. The combined organic phases were diluted with hexanes and washed with brine and water, dried (Na2SO4) and concentrated to give the title compound as an amber oil (4 g, 44%): 1H NMR (300 MHz, CDCl3) δ 8.46 (d, J=2.7 Hz, 1H), 7.73-7.62 (m, 2H), 7.52 (dd, J=8.6, 0.6 Hz, 1H), 7.48-7.35 (m, 2H), 7.13-7.02 (m, 2H), 6.92-6.80 (m, 1H), 6.75 (ddd, J=10.0, 8.9, 2.5 Hz, 1H), 3.46 (d, J=5.1 Hz, 1H), 3.03-2.96 (m, 1H); ESIMS m/z 401 ([M+H]+).

Provenance & Evidence