Benzyl Bromide → 1-[2-(Benzyloxy)-5-bromophenyl]ethan-1-one

Participants

Reaction Steps

To a mixture of 1-(5-bromo-2-hydroxyphenyl)ethanone (505 mg, 2.348 mmol) and cesium carbonate (1339 mg, 4.11 mmol) in DMF (5 ml) was added benzyl bromide (0.351 ml, 2.94 mmol) and the resulting mixture was stirred overnight. The reaction mixture was diluted with EtOAc and washed 2 times with water, followed by brine. The organic layer was dried over sodium sulfate, filtered, and the solvent was evaporated under reduced pressure. The residue was purified by flash column chromatography on silica gel, eluting with EtOAc in hexanes to afford 709 mg of 1-[2-(benzyloxy)-5-bromophenyl]ethanone, 703 mg (2.304 mmol) of which were combined with BISPIN (731 mg, 2.88 mmol), PdCl2(dppf) (202 mg, 0.276 mmol), and potassium acetate (452 mg, 4.61 mmol) in 1,4-dioxane (2 ml)/DMSO (10 ml). The mixture was heated at 80° C. overnight. The solids were filtered through a silica plug washing with EtOAc. Water was added and the filtrate was extracted 3 times with EtOAc. The combined organics were washed with brine, dried over sodium sulfate, and concentrated. The residue was purified by flash column chromatography on silica gel, eluting with EtOAc in hexanes to afford 634 mg of 1-[2-(benzyloxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]ethanone. A mixture of 64 mg (0.182 mmol) of 1-[2-(benzyloxy)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]ethanone, 63 mg (0.105 mmol) of (4S,5R)-3-{[6-azetidin-1-yl-3-(5-chloro-2-methoxyphenyl)pyridin-2-yl]methyl}-5-[3,5-bis(trifluoromethyl)phenyl]-4-methyl-1,3-oxazolidin-2-one (EXAMPLE 27), potassium carbonate (1M aqueous) (0.400 ml, 0.400 mmol), and 1,1′-bis(di-t-butylphosphino)ferrocene palladium dichloride (15 mg, 0.023 mmol) in 1,4-dioxane (1.5 ml) was heated at 120° C. with microwaves for 4 hours, then transferred to an oil bath at 120° C. overnight. The mixture was filtered through a silica plug, washing with EtOAc. The filtrate was concentrated and purified by flash column chromatography on silica gel, eluting with EtOAc in hexanes to afford the title compound. Mass spectrum (ESI) 790.6 (M+1).

Provenance & Evidence