反应详情

温度

110 °C

A mixture of tert-butyl (3-bromo-2-chloro-5-cyanophenyl)carbamate (116 mg, 0.349 mmol), (+/−)-4-((3R,4R)-3-((tert-butyldimethylsilyl)oxy)piperidin-4-yl)morpholine (100 mg, 0.333 mmol), Pd2 dba3 (9.14 mg, 9.98 mmol), 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (18.65 mg, 0.030 mmol), and cesium carbonate (217 mg, 0.666 mmol) in Dioxane (2 mL) was evacuated and filled with nitrogen three times and heated at 110° C. overnight. The reaction mixture was diluted with dichloromethane and filtered through Celite, the filtrate was concentrated and the crude product was purified by flash chromatography on silica gel using an automated ISCO system (24 g column, eluting with 5-25% ethyl acetate/hexanes). (+/−)-tert-butyl (3-((3R,4R)-3-((tert-butyldimethylsilyl)oxy)-4-morpholinopiperidin-1-yl)-2-chloro-5-cyanophenyl)carbamate (138 mg) was obtained as a white solid.

1. customwas evacuated
2. additionfilled with nitrogen three times
3. additionThe reaction mixture was diluted with dichloromethane
4. filtrationfiltered through Celite
5. concentrationthe filtrate was concentrated
6. customthe crude product was purified by flash chromatography on silica gel using
7. washan automated ISCO system (24 g column, eluting with 5-25% ethyl acetate/hexanes)