反応 #433
ord-e7f2690304e449cfaae6138b77013850
反応条件
実験手順
PdOAc2 (0.124 g, 0.55 mmol) and dicyclohexyl(2',4',6'-triisopropylbiphenyl-2-yl)phosphine (0.263 g, 0.55 mmol) were added in one portion to a degassed solution of 1-(benzyloxy)-4-bromo-2-fluorobenzene (1.550 g, 5.51 mmol), (R)-2-(tert- butyldimethylsilyloxy)propan-1-amine (1.044 g, 5.51 mmol) and cesium carbonate (2.69 g, 8.27 mmol) in toluene (20 mL) at 20°C in a microwave vial. The microwave vial was sealed and the reaction was heated to 120 °C for 10 hours in the microwave reactor and cooled to RT. **** The reaction was incomplete so the reaction was heated to 120 °C for 2 hours in the microwave reactor and cooled to RT. The reaction was incomplete and further PdOAc2 (0.124 g, 0.55 mmol) and dicyclohexyl(2',4',6'-triisopropylbiphenyl-2-yl)phosphine (0.263 g, 0.55 mmol) was added and the suspension was stirred at 120 °C for a further 6 hours in the microwave reactor and cooled to RT. The reaction mixture was diluted with EtOAc (50 mL), and washed sequentially with water (50 mL) and saturated brine (50 mL). The organic layer was filtered and dried over Na2SO4, filtered and evaporated to afford crude product. The crude product was taken up in DCM (20 mL) and an isoluble white solid EN04063-48-1 (1.45 g, 3.72 mmol, 67.5 %) was filtered off (not product). The filtrate was evaporated and was purified by flash silica chromatography, elution gradient 0 to 30% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford (R)-4-(benzyloxy)-N-(2-(tert-butyldimethylsilyloxy)propyl)-3-fluoroaniline (1.450 g, 67.5 %) as a yellow oil. **** Reaction is slow if done on 1.5g scale in a 20 ml reaction vial. Next time do 1g reaction per 20 ml vial. See EN04063-50