Reaction #533
ord-c3293297b4c643b7b38f6be28fe8ecb0
Reaction equation
Solvents
Conditions
Procedure
PdOAc2 (0.030 g, 0.13 mmol) and dicyclohexyl(2',4',6'-triisopropylbiphenyl-2-yl)phosphine (0.064 g, 0.13 mmol) were added in one portion to a degassed solution of 4'-bromo-2,6-difluorobiphenyl (0.36 g, 1.34 mmol), (R)-2-(tert- butyldimethylsilyloxy)propan-1-amine (0.355 g, 1.87 mmol) and cesium carbonate (0.654 g, 2.01 mmol) in toluene (10 mL) at 20°C under nitrogen. The resulting suspension was stirred at 120 °C for 50 hours. The reaction mixture was diluted with EtOAc (150 mL) and water (150 mL) and the biphasic mixture was filtered through celite. The organic layer was separated and washed sequentially with water (150 mL) and saturated brine (150 mL). The organic layer was evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution gradient 0 to 10% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford (R)-N-(2-(tert-butyldimethylsilyloxy)propyl)-2',6'-difluorobiphenyl-4-amine (0.300 g, 59.4 %) as a yellow solid.