Sodium Carbonate → (S)-3-(4-(2-bromo-5-fluoropyridin-4-yl)phenyl)-5,5-dimethyl-4-phenyloxazolidin-2-one

Participants

Reaction Conditions

Reaction Steps

A microwave vial was charged with (S)-3-(4-iodophenyl)-5,5-dimethyl-4-phenyloxazolidin-2-one (Intermediate C)(0.200 g, 0.509 mmol), 2-bromo-5-fluoropyridine-4-boronic acid (commercially available from Combi Blocks, San Diego, Calif.) (0.224 g, 1.017 mmol), sodium carbonate (0.162 g, 1.526 mmol), dioxane (3.0 mL), and water (0.60 mL). Dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium (II) (DCM adduct)(0.042 g, 0.051 mmol) was added, the system was purged with argon, and the tube was sealed. The mixture was then stirred at 100° C. in the microwave for 1 hour. Additional 2-bromo-5-fluoropyridine-4-boronic acid (0.224 g, 1.017 mmol) and dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium (II) DCM adduct (0.042 g, 0.051 mmol) were added, the system was purged with argon, and the tube was sealed. The resulting mixture was then stirred at 100° C. in a microwave for 1 hour. Additional 2-bromo-5-fluoropyridine-4-boronic acid (0.224 g, 1.017 mmol) and dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium (II) DCM adduct (0.042 g, 0.051 mmol) were added, the system was purged with argon, and the tube was sealed. The resulting mixture was stirred at 100° C. in a microwave for 1 hour. The reaction mixture was then filtered through Celite® brand filter aid and the filtrate was concentrated to afford a dark brown oil. The oil thus obtained was purified using column chromatography on silica gel (RediSep 40 g column, gradient elution with 0-50% EtOAc-hexane) to afford (S)-3-(4-(2-bromo-5-fluoropyridin-4-yl)phenyl)-5,5-dimethyl-4-phenyloxazolidin-2-one (0.062 g, 0.140 mmol, 28% yield) as an off-white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.92 (s, 3H), 1.65 (s, 3H), 5.53 (s, 1H), 7.17-7.49 (m, 5H), 7.59-7.73 (m, 4H), 7.83 (d, J=5.97 Hz, 1H), 8.48 (d, J=2.35 Hz, 1H). m/z (ESI) 441 (M+H)+.

Provenance & Evidence