反应详情

温度

60 °C

To 300.0 mg (0.49 mmol) tert-butyl 4-{3-[(3R)-3-{[1-(5-bromopyridin-3-yl)-3-methoxy-3-oxopropyl]carbamoyl}piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate (example 8c) in 12 ml toluene were added 11.4 mg (0.01 mmol) tetrakis(triphenylphosphine)palladium(0), 97.4 mg (0.59 mmol) (4-cyano-3-fluoro-phenyl)boronic acid in 3.0 ml ethanol and 57.2 mg (0.98 mmol) potassium fluoride in 3.0 ml water. The mixture was stirred at 100° C. for 10 hours and at 60° C. for 20 hours, diluted with water and extracted with ethyl acetate and sodium hydrogen carbonate solution. The organic phase was dried over sodium sulfate and concentrated in vacuum. Chromatography over 10 g silica gel (dichloromethane/ethanol 100/0-95/5-90/10) gave 157 mg (44%) tert-butyl 4-{3-[(3R)-3-({1-[5-(4-cyano-3-fluorophenyl)pyridin-3-yl]-3-methoxy-3-oxopropyl}carbamoyl)piperidin-1-yl]-3-oxopropyl}piperidine-1-carboxylate.

1. extractionextracted with ethyl acetate and sodium hydrogen carbonate solution
2. dry with materialThe organic phase was dried over sodium sulfate
3. concentrationconcentrated in vacuum