Ammonium Hydroxide → 4,4-Difluorocyclohexanecarboxamide

Participants

Reaction Steps

A solution of 4,4-difluorocyclohexanecarboxylic acid (0.217 g, 1.322 mmol) in DCM (4 mL) was treated with oxalyl chloride (0.174 mL, 1.983 mmol) followed by catalytic DMF (1 drop) and the mixture stirred at RT for 1.5 h. The mixture was concentrated to dryness, co-evaporated with DCM (1×) and the resulting residue dissolved in THF (2 mL), added to a stirring solution of NH4OH (˜14M, 2 mL, 28.0 mmol) in THF (2 mL) and stirred for 30 minutes. The mixture was diluted with brine, extracted with EtOAc (3×) and the combined organics were dried over MgSO4 and concentrated to dryness to afford 4,4-difluorocyclohexanecarboxamide (167 mg, 77%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 7.28 (s, 1H), 6.79 (s, 1H), 2.20 (m, 1H), 2.00 (m, 2H), 1.86-1.67 (m, 4H), 1.57 (m, 2H).

Provenance & Evidence