反应详情

温度

60 °C

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).

1. additionAfter the addition
2. temperatureThe reaction solution was cooled to 0° C.
3. customquenched by saturated NH4Cl aq. solution
4. extractionextracted with EtOAC (50 m×3)
5. washThe combined organic layer was washed with brine
6. dry with materialdried over Na2SO4
7. concentrationconcentrated
8. customto get the crude product, which
9. customwas purified by column chromatography on silica gel (Petroleum ether: EtOAc=4:1˜2:1)