反应详情

温度

6 °C

(1-Oxypyridin-3-yl)acetonitrile (I115) (4.00 g, 29.8 mmol) was added slowly to a stirred solution of POCl3 (50 mL). The mixture was heated to 80° C. in 5-7° C. increments every 10-15 minutes. The reaction was then heated at reflux for 3 hours. Excess POCl3 was removed by distillation and the brown residue carefully poured on to cold water (200 mL). A saturated solution NaHCO3 (300 mL) was then added carefully. Solid NaHCO3 was added in portions to the aqueous mixture until the evolution of gas ceased. The aqueous layer was separated in to two portions (250 mL each) and each portion was extracted with EtOAc (3×100 mL). The combined organic layers were washed with brine (200 mL) and dried over Na2SO4. The solvent was removed and the residue purified by column chromatography on silica gel (0-100% EtOAc in petroleum benzine) to afford a mixture of two isomeric compounds. The mixture was re-purified by column chromatography on silica gel (0-40% diethyl ether in petroleum benzine 40-60° C.) to afford the title compound (I116) (0.932 g, 20%) as a white solid; 1H NMR (400 MHz, CDCl3) δ 8.41 (dd, J=4.8, 1.8 Hz, 1H), 7.90 (ddt, J=7.6, 1.7, 0.7 Hz, 1H), 7.34 (dd, J=7.6, 4.8 Hz, 1H), 3.87 (s, 2H). LCMS Method C: rt 4.50 min; m/z 153 [M+H]+.

1. temperatureThe reaction was then heated
2. temperatureat reflux for 3 hours
3. customExcess POCl3 was removed by distillation
4. additionthe brown residue carefully poured on to cold water (200 mL)
5. additionA saturated solution NaHCO3 (300 mL) was then added carefully
6. additionSolid NaHCO3 was added in portions to the aqueous mixture until the evolution of gas
7. customThe aqueous layer was separated in to two portions (250 mL each)
8. extractioneach portion was extracted with EtOAc (3×100 mL)
9. washThe combined organic layers were washed with brine (200 mL)
10. dry with materialdried over Na2SO4
11. customThe solvent was removed
12. customthe residue purified by column chromatography on silica gel (0-100% EtOAc in petroleum benzine)
13. customto afford
14. additiona mixture of two isomeric compounds
15. customThe mixture was re-purified by column chromatography on silica gel (0-40% diethyl ether in petroleum benzine 40-60° C.)