1-(Benzyloxy)-4-bromo-2-fluorobenzene → (R)-4-(benzyloxy)-N-(2-(tert-butyldimethylsilyloxy)propyl)-3-fluoroaniline

Temperature

120 °C

PdOAc2 (0.799 g, 3.56 mmol) and dicyclohexyl(2',4',6'-triisopropylbiphenyl-2-yl)phosphine (1.696 g, 3.56 mmol) were added in one portion to a degassed solution of 1-(benzyloxy)-4-bromo-2-fluorobenzene (10.00 g, 35.57 mmol), 1-(benzyloxy)-4-bromo-2-fluorobenzene (10.00 g, 35.57 mmol) and cesium carbonate (17.39 g, 53.36 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 10 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 water (150 mL). 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 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 (10.10 g, 72.9 %) as a orange oil.

ORD record

ord-5baedbe69f7740f6b5f0fde32453a3b3

Source dataset

750 AstraZeneca ELN dataset

Original link

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