5-Bromo-2-methoxybenzonitrile → (R)-5-(2-(tert-butyldimethylsilyloxy)propylamino)-2-methoxybenzonitrile

Participants

Reaction Conditions

Reaction Steps

Reaction carried PdOAc2 (0.476 g, 2.12 mmol) and dicyclohexyl(2',4',6'-triisopropylbiphenyl-2-yl)phosphine (1.012 g, 2.12 mmol) were added in one portion to a degassed solution of 5-bromo-2-methoxybenzonitrile (4.50 g, 21.22 mmol), (R)-2-(tert- butyldimethylsilyloxy)propan-1-amine (4.82 g, 25.47 mmol) and cesium carbonate (10.37 g, 31.83 mmol) in toluene (100 mL) at 20°C in a microwave vial. The microwave vial was sealed and the reaction was heated to 120 °C for 12 hours in the microwave reactor and cooled to RT. The reaction mixture was diluted with EtOAc (100 mL) and water (100 mL). The biphasic mixture was filtered through celite. The organic layer was separated and washed sequentially with water (100 mL) and saturated brine (100 mL). The organic layer was filtered and dried over Na2SO4, filtered and evaporated to afford crude product. The crude product was evaporated and was purified by flash silica chromatography, elution gradient 0 to 20% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford (R)-4-(benzyloxy)-N-(2-(tert- butyldimethylsilyloxy)propyl)-3-fluoroaniline (0.851 g, 61.4 %) as a orange oil.

Provenance & Evidence