反应详情

A solution of 1-(difluoromethyl)-1H-pyrazole-3-carboxylic acid (238 mg, 1.47 mmol) in methanol (9 mL) was cooled to 0° C. and treated with concentrated sulfuric acid (98%, 0.10 mL, 1.8 mmol). The reaction mixture was heated at reflux for 2 hours, whereupon it was cooled, concentrated in vacuo, and partitioned between ethyl acetate (15 mL) and water (15 mL). The organic layer was washed with water (3×10 mL) until the water washes reached pH 4-5, then washed with saturated aqueous sodium bicarbonate solution (10 mL), dried over sodium sulfate, filtered, and concentrated under reduced pressure. The product was obtained as a clear, colorless oil. Yield: 241 mg, 1.37 mmol, 93%. LCMS m/z 177.0 [M+H]+. 1H NMR (400 MHz, CDCl3) δ 7.89 (d, J=2.7 Hz, 1H), 7.28 (t, JHF=60.0 Hz, 1H), 6.99 (d, J=2.6 Hz, 1H), 3.98 (s, 3H).

1. temperatureThe reaction mixture was heated
2. temperatureat reflux for 2 hours, whereupon it
3. temperaturewas cooled
4. concentrationconcentrated in vacuo
5. custompartitioned between ethyl acetate (15 mL) and water (15 mL)
6. washThe organic layer was washed with water (3×10 mL) until the water washes
7. washwashed with saturated aqueous sodium bicarbonate solution (10 mL)
8. dry with materialdried over sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated under reduced pressure
11. customThe product was obtained as a clear, colorless oil