反应详情

温度

0 °C

(+/−)-N-((3R,4R)-1-(3-amino-2-chloro-5-cyanophenyl)-3-hydroxypiperidin-4-yl)-2-chloroacetamide (549 mg, 1.600 mmol) was dissolved in anhydrous THF. The solution was cooled to 0° C. sodium hydride (96 mg, 2.399 mmol) and tetrabutylammonium bromide (77 mg, 0.240 mmol) were added (briefly opening the reaction flask to air). The reaction mixture was stirred at 0° C. for 5 minutes, then the ice bath was removed and the mixture stirred at room temperature for 1.5 hours. The reaction was quenched with aq. NH4Cl solution. The reaction mixture was partitioned between water and EtOAc. The organic layer was washed with brine (+small amount of NaHCO3 solution), then dried over MgSO4. The organic layer was filtered and evaporated to dryness to give 0.85 g crude colorless solid, which was purified via silica gel chromatography: gradient from 100% DCM to 100% EtOAc, then isocratic at 100% EtOAc to afford (+/−)-3-amino-4-chloro-5-((4aR,8aR)-2-oxohexahydro-1H-pyrido[3,4-b][1,4]oxazin-6(7H)-yl)benzonitrile (197 mg).

1. additionwere added (
2. customthe ice bath was removed
3. stirringthe mixture stirred at room temperature for 1.5 hours
4. customThe reaction was quenched with aq. NH4Cl solution
5. customThe reaction mixture was partitioned between water and EtOAc
6. washThe organic layer was washed with brine (+small amount of NaHCO3 solution),
7. dry with materialthen dried over MgSO4
8. filtrationThe organic layer was filtered
9. customevaporated to dryness
10. customto give 0.85 g crude colorless solid, which
11. customwas purified via silica gel chromatography