(Diethylamino)sulfur trifluoride → HCID 68380276, compound

Participants

Reaction Conditions

Reaction Steps

Synthesis of benzyl 2-(3,3-difluorocyclobutyl)-4-fluorophenyl ether (C20). A solution of 3-[2-(benzyloxy)-5-fluorophenyl]cyclobutanone (C19) (600 mg, 2.22 mmol) in dichloromethane (20 mL) cooled to −78° C. was treated with (diethylamino)sulfur trifluoride (753 mg, 4.44 mmol) over a period of 5 minutes. The mixture was stirred at −78° C. for 30 minutes, whereupon it was allowed to warm to room temperature and stirring was continued for 16 hours. The mixture was cooled to −78° C. and a saturated aqueous sodium bicarbonate solution (10 mL) was added. The mixture was allowed to warm to room temperature and additional saturated aqueous sodium bicarbonate solution (50 mL) was added, followed by extraction with dichloromethane (2×50 mL). The combined organic layers were washed with saturated aqueous sodium chloride solution (50 mL), dried over magnesium sulfate, and concentrated in vacuo. Purification via silica gel chromatography (Gradient: 0% to 25% ethyl acetate in heptanes) afforded the desired title compound as a colorless oil. Yield: 315 mg, 108 mmol, 48%. GCMS m/z 292 (M+). 1H NMR (400 MHz, CDCl3) δ 2.58-2.73 (m, 2H), 2.90-3.03 (m, 2H), 3.53-3.64 (m, 1H), 5.06 (s, 2H), 6.83-6.94 (m, 3H), 7.34-7.45 (m, 5H).

Provenance & Evidence