反应详情

温度

100 °C

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)+.

1. customthe system was purged with argon
2. customthe tube was sealed
3. customthe system was purged with argon
4. customthe tube was sealed
5. stirringThe resulting mixture was then stirred at 100° C. in a microwave for 1 hour
6. customthe system was purged with argon
7. customthe tube was sealed
8. stirringThe resulting mixture was stirred at 100° C. in a microwave for 1 hour
9. filtrationThe reaction mixture was then filtered through Celite® brand
10. filtrationfilter aid
11. concentrationthe filtrate was concentrated
12. customto afford a dark brown oil
13. customThe oil thus obtained
14. customwas purified