反应详情

温度

85 °C

To a solution of methyl 2-cyano-3-fluoro-6-methylbenzoate (208 mg, 1.07 mmol) in methyl pivalate (2 mL), N-bromosuccinimide (310 mg, 1.74 mmol) and benzoylperoxide (20 mg, 0.097 mmol) were added. The reaction mixture was stirred at 85° C. under nitrogen atmosphere for 3 hours. Crude was filtered on Gooch and washed with toluene. Volatiles were evaporated and the residue was dissolved in acetonitrile (3 mL). Triethylamine (0.41 mL, 2.9 mmol) and 1-(4,4-difluorocyclohexyl)-piperidin-4-ylamine (280 mg, 0.97 mmol) were added and the reaction mixture was stirred at 90° C. for 3 hours. Crude was diluted with dichloromethane and washed with 15% ammonium hydroxide Organic phase was dried over sodium sulfate, filtered and evaporated. Column chromatography (dichloromethane/ethanol:95/5) afforded title compound (222 mg, 60% yield).

1. filtrationCrude was filtered on Gooch
2. washwashed with toluene
3. customVolatiles were evaporated
4. dissolutionthe residue was dissolved in acetonitrile (3 mL)
5. stirringthe reaction mixture was stirred at 90° C. for 3 hours
6. washwashed with 15% ammonium hydroxide Organic phase
7. dry with materialwas dried over sodium sulfate
8. filtrationfiltered
9. customevaporated