Ammonium Hydroxide → 4,4-Difluorocyclohexanecarboxamide

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).

1. concentrationThe mixture was concentrated to dryness, co-evaporated with DCM (1×)
2. dissolutionthe resulting residue dissolved in THF (2 mL)
3. stirringstirred for 30 minutes
4. extractionextracted with EtOAc (3×)
5. dry with materialthe combined organics were dried over MgSO4
6. concentrationconcentrated to dryness

ORD record

ord-e481285497f24033a19702b19b09a06e

Source dataset

uspto-grants-2016_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09382228B2