反应详情

Add (±)-3,3,4,4,4-pentafluoro-2-butanol (710 mg, 4.3 mmol) slowly to a slurry of sodium hydride (104 mg, 1.2 equiv, 60% mineral oil, washed with hexane) in hexamethylphosphoramide (2 mL) under nitrogen at 0° C. Allow the slurry to warm to ambient temperature and stir for 5 min. Add 5-chloro-pyridine-2-carbonitrile (300 mg, 2.2 mmol), then heat the mixture in a sealed flask at 130° C. for 4 h (monitor reaction by GC/MS). Cool the reaction to room temperature, adjust the mixture to pH 9 with saturated aqueous Na2CO3, then extract with diethyl ether (2×50 mL). Dry the combined organic extracts over Na2SO4, filter and concentrate in vacuo. Purify the crude mixture by chromatography on silica gel eluting with hexane/EtOAc (19:1 to 7:3 gradient) to obtain the desired intermediate (380 mg, 66%). GC-MS m/z: 266 (M+).

1. custom(monitor reaction by GC/MS)
2. temperatureCool
3. customthe reaction to room temperature
4. extractionextract with diethyl ether (2×50 mL)
5. dry with materialDry the combined organic extracts over Na2SO4
6. filtrationfilter
7. concentrationconcentrate in vacuo
8. customPurify the crude mixture by chromatography on silica gel eluting with hexane/EtOAc (19:1 to 7:3 gradient)