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

Participants

Reaction Conditions

Reaction Steps

PdOAc2 (0.399 g, 1.78 mmol) and dicyclohexyl(2',4',6'-triisopropylbiphenyl-2-yl)phosphine (0.848 g, 1.78 mmol) were added in one portion to a degassed solution of 1-(benzyloxy)-4-bromo-2-fluorobenzene (5.00 g, 17.79 mmol), 2-(tert- butyldimethylsilyloxy)ethanamine (4.16 g, 17.79 mmol) and cesium carbonate (8.69 g, 26.68 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 10 hours in the microwave reactor and cooled to RT. **** _Split into 5 x 20 ml mw vials such as in each was:_ PdOAc2 (0.080 g, 0.36 mmol) and dicyclohexyl(2',4',6'-triisopropylbiphenyl-2-yl)phosphine (0.170 g, 0.36 mmol) were added in one portion to a degassed solution of 1-(benzyloxy)-4-bromo-2-fluorobenzene (1.000 g, 3.56 mmol), 2-(tert- butyldimethylsilyloxy)ethanamine (0.832 g, 3.56 mmol) and cesium carbonate (1.739 g, 5.34 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 mixtures were combined and diluted with EtOAc (150 mL), and washed sequentially with water (200 mL) and saturated brine (200 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 30% EtOAc in isohexane. Pure fractions were evaporated to dryness to afford 4-(benzyloxy)-N-(2-(tert- butyldimethylsilyloxy)ethyl)-3-fluoroaniline (3.62 g, 54.2 %) as a yellow oil.

Provenance & Evidence