(Diethylamino)sulfur trifluoride → HCID 68380276, compound

Temperature

-78 °C

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).

1. temperatureto warm to room temperature
2. stirringstirring
3. waitwas continued for 16 hours
4. temperatureThe mixture was cooled to −78° C.
5. temperatureto warm to room temperature
6. extractionfollowed by extraction with dichloromethane (2×50 mL)
7. washThe combined organic layers were washed with saturated aqueous sodium chloride solution (50 mL)
8. dry with materialdried over magnesium sulfate
9. concentrationconcentrated in vacuo
10. customPurification via silica gel chromatography (Gradient: 0% to 25% ethyl acetate in heptanes)

ORD record

ord-6a6d68458fea406fa960aea70bcc6145

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08697673B2