(2-Aminoethoxy)(tert-butyl)dimethylsilane → 4-(benzyloxy)-N-(2-(tert-butyldimethylsilyloxy)ethyl)-3-fluoroaniline

Participants

Reaction Conditions

Reaction Steps

PdOAc2 (42.3 mg, 0.19 mmol) and dicyclohexyl(2',4',6'-triisopropylbiphenyl-2-yl)phosphine (90 mg, 0.19 mmol) were added in one portion to a degassed solution of 1-(benzyloxy)-4-bromo-2-fluorobenzene (530 mg, 1.89 mmol), 2-(tert- butyldimethylsilyloxy)ethanamine (441 mg, 1.89 mmol) and cesium carbonate (921 mg, 2.83 mmol) in toluene (15 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 (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 purified by flash silica chromatography, elution gradient 0 to 30% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford 4-(benzyloxy)-N-(2-(tert- butyldimethylsilyloxy)ethyl)-3-fluoroaniline (312 mg, 44.1 %) as a yellow oil.

Provenance & Evidence