反应详情

Heat a mixture of 2-bromo-6-(1-t-butoxycarbonylpiperidin-4-ylcarbonyl)-pyridine (152 mg, 0.41 mmol), N-methyl-2,4,6-trifluorobenzamide (92.6 mg, 0.49 mmol), Pd2(dba)3 (9.2 mg, 0.01 mmol), BINAP (12.4 mg, 0.02 mmol), sodium t-butoxide (55 mg, 0.57 mmol) in anhydrous toluene (10 mL) at 85° C. for 16 hrs. Cool the reaction to room temperature and add another aliquot of N-methyl-2,4,6-trifluorobenzamide, Pd2(dba)3, BINAP and sodium t-butoxide in the same amount. Re-heat the reaction at 85° C. for 16 more hours. Extract the reaction mixture with ethyl acetate and aqueous NaOH (0.1 N). Collect and dry the organic layers. Concentrate and purify the crude product by chromatography (silica gel, 10% -30% ethyl acetate/hexane) to obtain 2,4,6-trifluoro-N-methyl-N-[6-(1-t-butoxycarbonyl-piperidin-4-ylcarbonyl)-pyridin-2-yl]-benzamide (86 mg, 44% yield).

1. temperatureHeat
2. temperatureCool
3. customthe reaction to room temperature
4. customRe-heat the reaction at 85° C. for 16 more hours
5. extractionExtract the reaction mixture with ethyl acetate and aqueous NaOH (0.1 N)
6. customCollect
7. customdry the organic layers
8. concentrationConcentrate
9. custompurify the crude product by chromatography (silica gel, 10% -30% ethyl acetate/hexane)