反应详情

温度

85 °C

To a solution of methyl 4-chloro-2-iodo-6-methylbenzoate (175 mg, 0.56 mmol) in methyl pivalate (1 mL), N-bromosuccinimide (120 mg, 0.67 mmol) and benzoylperoxide (14 mg, 0.06 mmol) were added. The reaction mixture was stirred at 85° C. under nitrogen atmosphere for 3 hours. Additional N-bromosuccinimide (60 mg) and benzoylperoxide (7 mg) were added and stirring continued for 1 hour. Crude was filtered on Gooch and washed with toluene. Volatiles were evaporated and the residue was dissolved in acetonitrile (2 mL). Triethylamine (0.28 mL, 2 mmol) and 1-(4,4-difluorocyclohexyl)-piperidin-4-ylamine (110 mg, 0.5 mmol) were added and the reaction mixture was stirred at 90° C. for 4 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:97/3) afforded title compound (116 mg, 45% yield).

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