反应详情

温度

50 °C

(4S,5R)-5-[3,5-Bis(trifluoromethyl)phenyl]-3-{[5-bromo-2-(methylsulfanyl)pyrimidin-4-yl]methyl}-4-methyl-1,3-oxazolidin-2-one (INTERMEDIATE 8, 2.0 g, 3.77 mmol), 5-isopropyl-2-methoxypyridin-3-ylboronic acid (1.25 g, 4.53 mmol) and K2CO3 (1.56 g, 11.31 mmol) were added to a round bottom flask, which was then evacuated and charged with nitrogen 3 times. THF (15 mL) and water (3 mL) were then added. After evacuating and charging again with nitrogen, 1,1′-bis(di-tert-butylphosphino)ferrocene palladium dichloride (0.369 g, 0.566 mmol) was added and the reaction heated for 60 minutes at 50° C., at which time LCMS showed complete conversion to product. The reaction was diluted with 50 mL ethyl acetate and poured into 100 mL saturated NH4Cl solution. The ethyl acetate layer was washed with brine (100 mL), then filtered through a 20 g plug of sodium sulfate, eluting with 50 mL ethyl acetate. The filtrate was concentrated prior to flash purification. The crude was purified by silica gel chromatography, eluting with a 0-20% ethyl acetate/hexanes gradient followed by isocratic elution at 20% ethyl acetate/hexanes. Pure fractions were concentrated to give product as colorless foam. LCMS (M+H)+: 601.4.

1. customwhich was then evacuated
2. additioncharged with nitrogen 3 times
3. additionTHF (15 mL) and water (3 mL) were then added
4. customAfter evacuating
5. additionwas added
6. washThe ethyl acetate layer was washed with brine (100 mL)
7. filtrationfiltered through a 20 g plug of sodium sulfate
8. washeluting with 50 mL ethyl acetate
9. concentrationThe filtrate was concentrated
10. customto flash purification
11. customThe crude was purified by silica gel chromatography
12. washeluting with a 0-20% ethyl acetate/hexanes gradient
13. washfollowed by isocratic elution at 20% ethyl acetate/hexanes
14. concentrationPure fractions were concentrated
15. customto give product as colorless foam