4,4-Difluorocyclohexanone → 2-(4,4-Difluorocyclohexylidene)-2-(2-methylpyrimidin-5-yl)acetonitrile

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-(2-methylpyrimidin-5-yl)acetonitrile (1 g, 7.52 mmol) and 4,4-difluorocyclohexanone (1.1 g, 8.27 mmol) in 1,4-dioxane (40 mL) was added t-BuOK (0.8 g, 8.27 mmol) in two portions. After the addition was completed, the reaction was heated to 60° C. and stirred overnight. The reaction solution was cooled to 0° C., quenched by saturated NH4Cl aq. solution and extracted with EtOAC (50 m×3). The combined organic layer was washed with brine, dried over Na2SO4 and concentrated to get the crude product, which was purified by column chromatography on silica gel (Petroleum ether: EtOAc=4:1˜2:1) to afford 2-(4,4-difluorocyclohexylidene)-2-(2-methylpyrimidin-5-yl)acetonitrile (440 mg, yield: 23.5%). 1H NMR (CDCl3 varian 400 MHz): δ8.61 (s, 2H), 2.97 (t, J=8.0 Hz, 2H), 2.80 (s, 3H), 2.55 (t, J=8.0 Hz, 2H), 2.27-2.17 (m, 2H), 2.09-1.98 (m, 2H).

Provenance & Evidence