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), (R)-2-(tert- butyldimethylsilyloxy)propan-1-amine (8.08 g, 42.69 mmol) and cesium carbonate (17.39 g, 53.36 mmol) in toluene (150 mL) at 20°C under nitrogen. The resulting suspension was stirred at 120 °C for 35 hours. The reaction mixture was diluted with EtOAc (150 mL) and water (150 mL) and 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 organic layer was evaporated to afford crude product. The crude product 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 (9.38 g, 67.7 %) as a orange oil. ****

ORD record

ord-13647a5d8826486e986a33a5850b535a

Source dataset

750 AstraZeneca ELN dataset

Original link

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