反应详情

温度

80 °C

Methyl 4-(4-chloro-2-fluorophenyl)nicotinate (50 mg, 0.188 mmol) in toluene (1 mL) was treated with cesium carbonate (92 mg, 0.282 mmol) and N-Boc-L-Leucinol (121 mg, 0.565 mmol). The mixture was purged with nitrogen gas for 5 min and treated with di-tert-butyl(2′,4′,6′-triisopropyl-[1,1′-biphenyl]-2-yl)phosphine (48.0 mg, 0.113 mmol). After purging the mixture with nitrogen for another 5 min, palladium(II)acetate (42.3 mg, 0.188 mmol) was added and nitrogen bubbled through for another 10 min. The mixture was sealed tightly and heated at 80° C. for 12 h. The mixture was filtered through a bed of diatomaceous earth (Celite®) and washed with ethyl acetate (2×3 mL). The washings were concentrated under reduced pressure. The residue was purified by combi flash (ethyl acetate and petroleum ether) to afford (S)-methyl 4-(4-((2-((tert-butoxycarbonyl)amino)-4-methylpentyl)oxy)-2-fluorophenyl)nicotinate (50 mg, 0.112 mmol, 60% yield). LC/MS (ESI) m/e 447.2 [(M+H)+, calcd for C24H32FN2O5 447.2]; LC/MS retention time (method C): tR=2.17 min.

1. customThe mixture was purged with nitrogen gas for 5 min
2. customAfter purging the mixture with nitrogen for another 5 min
3. customnitrogen bubbled through for another 10 min
4. customThe mixture was sealed tightly
5. filtrationThe mixture was filtered through a bed of diatomaceous earth (Celite®)
6. washwashed with ethyl acetate (2×3 mL)
7. concentrationThe washings were concentrated under reduced pressure
8. customThe residue was purified by combi flash (ethyl acetate and petroleum ether)