反应详情

Add 2-trifluoromethyl-2-propanol (1.1 g, 8.3 mmol) slowly to a slurry of sodium hydride (202 mg, 60% mineral oil, washed with hexane) in HMPA (3 mL) under nitrogen. Stir the slurry for 15 min, then add 5-fluoro-pyridine-2-carbonitrile (510 mg, 4.2 mmol). Stir the slurry for 16 h at ambient temperature. Adjust the mixture to pH 9 with sodium carbonate then extract with diethyl ether (3×50 mL). Collect the organic layer, dry over Na2SO4 and concentrate in vacuo. Purify by chromatography on silica gel eluting with hexane/EtOAc (95/5 to 80/20) to obtain the desired intermediate (768 mg, 79%). GC-MS m/z: 230 (Me).

1. stirringStir the slurry for 16 h at ambient temperature
2. extractionthen extract with diethyl ether (3×50 mL)
3. customCollect the organic layer
4. dry with materialdry over Na2SO4
5. concentrationconcentrate in vacuo
6. customPurify by chromatography on silica gel eluting with hexane/EtOAc (95/5 to 80/20)