Diethyl Ether → 1-(4,4-Difluorocyclohexyl)ethan-1-one

Participants

Reaction Steps

To a clear solution of 4,4-difluorocyclohexanecarboxylic acid (2.00 g, 12.18 mmol) in 100 mL THF at 0° C. was added slowly dropwise methyllithium, 1.6M solution in diethyl ether (30.5 mL, 48.7 mmol) from an addition funnel. The resulting cloudy mixture was allowed to stir 2 h, then was treated with chlorotrimethyl silane (24.74 mL, 195 mmol) dropwise over 10 min. The bath was removed and the clear solution allowed to stir 1 h. 5 mL 1M HCl aq. Was added and the reaction mixture stirred an additional hour. The reaction mixture was then concentrated in vacuo to a small volume, diluted with Et2O, and the organic layer was washed with water, sat'd aq. NaHCO3, brine, dried over magnesium sulfate, filtered, and concentrated in vacuo to give impure 1-(4,4-difluorocyclohexyl)-ethanone as a clear/colorless oil, which was used without further purification.

Provenance & Evidence