反应详情

温度

60 °C

Isopropyl iodide (1.225 g, 7.21 mmol) was added to a solution of ethyl 3-(trifluoromethyl)-1H-pyrazole-4-carboxylate (500 mg, 2.402 mmol) and DIEA (652 mg, 5.04 mmol) in DMF (5 mL) and the reaction stirred at RT for 3 h and 60° C. for 3 h. The reaction was diluted with ethyl acetate (30 mL), washed with 5% citric acid (30 mL), saturated sodium bicarbonate (30 mL) and brine (30 mL), dried (Na2SO4) and concentrated in vacuo to give an oil. LC and LCMS showed starting material still present (˜40%). The oil was dissolved in DMF (4 mL), treated with DIEA (652 mg, 5.04 mmol), isopropyliodide (1.22 g, 7.21 mmol) and catalytic 4-dimethylaminopyridine (˜5 mg) and stirred at RT overnight. The reaction was diluted with ethyl acetate (30 mL), washed with 5% citric acid (30 mL) saturated sodium bicarbonate (30 mL) and brine (30 mL), dried Na2SO4), concentrated in vacuo and purified by column chromatography (ethyl acetate/hexane) to afford ethyl 1-isopropyl-3-(trifluoromethyl)-1H-pyrazole-4-carboxylate (266 mg, 44% yield). 1H NMR (300 MHz, DMSO-d6): δ 1.26 (s, 9 H), 1.43 (d, 6 H), 4.23 (q, 2 H), 4.64 (hp, 1 H), 8.62 (s, 1 H); MS (ESI) m/z: 251.0 (M+H+).

1. washwashed with 5% citric acid (30 mL), saturated sodium bicarbonate (30 mL) and brine (30 mL)
2. dry with materialdried (Na2SO4)
3. concentrationconcentrated in vacuo
4. customto give an oil
5. stirringstirred at RT overnight
6. washwashed with 5% citric acid (30 mL) saturated sodium bicarbonate (30 mL) and brine (30 mL), dried Na2SO4),
7. concentrationconcentrated in vacuo
8. custompurified by column chromatography (ethyl acetate/hexane)