反应详情

Intermediate (h) (11 g, 49 mmol) was azeotroped×2 with toluene. Anhydrous acetonitrile (250 mL) and POCl3 (25 mL, 270 mmol) were added and the mixture was refluxed for about 2.5 h. Additional POCl3 (50 mL) was added and the mixture was refluxed for an additional 2 h. The volatile components were concentrated under vacuum at 40° C. to give a red solution. A minimum amount of dry acetonitrile was added until the solution was readily transferable whereupon it was poured onto ice in a large beaker. The flask was further rinsed with a small amount of acetonitrile which was added to the ice. Water (about 50 mL) was added to the ice mixture to help it with stirring. Concentrated NH4OH (25 mL) was added slowly with stirring until the ice slurry mixture was strongly basic, then 50% aqueous NaOH (25 mL) was also added to the still stirring slurry of ice. Additional ice was added. After about 5 minutes stirring as ice slurry, EtOAc was added. After stirring in the beaker for several more minutes, water was added to help melt the ice. The mixture was poured into a separatory funnel and the layers were allowed to partition. The aqueous layer was extracted with EtOAc×3. The combined EtOAc extracts were washed ×2 with saturated aqueous KHSO4, ×2 with saturated aqueous NaHCO3, ×1 with brine, dried over Na2SO4, filtered and evaporated to afford a pale pink powder which was triturated with ethyl acetate to give compound I(C) as pale pink solids (6.8 g, 28 mmol) in 57% yield. HPLC/LCMS purity was greater than 90%. 1H NMR (400 MHz, DMSO-D6) δ ppm 7.20 (s, 2H), 4.48 (s, 2H), 4.45 (s, 2H), 4.17-4.08 (m, 2H), 1.24 (t, 3H). LCMS (M+H)+: 243.2, 245.2.

1. temperaturethe mixture was refluxed for about 2.5 h
2. temperaturethe mixture was refluxed for an additional 2 h
3. concentrationThe volatile components were concentrated under vacuum at 40° C.
4. customto give a red solution
5. additionwas poured onto ice in a large beaker
6. washThe flask was further rinsed with a small amount of acetonitrile which
7. additionwas added to the ice
8. additionWater (about 50 mL) was added to the ice mixture
9. additionConcentrated NH4OH (25 mL) was added slowly
10. stirringwith stirring until the ice slurry mixture
11. addition50% aqueous NaOH (25 mL) was also added to the
12. stirringstill stirring slurry of ice
13. additionAdditional ice was added
14. stirringAfter about 5 minutes stirring as ice slurry, EtOAc
15. additionwas added
16. stirringAfter stirring in the beaker for several more minutes
17. additionwater was added
18. additionThe mixture was poured into a separatory funnel
19. customto partition
20. extractionThe aqueous layer was extracted with EtOAc×3
21. washThe combined EtOAc extracts were washed ×2 with saturated aqueous KHSO4, ×2 with saturated aqueous NaHCO3, ×1 with brine
22. dry with materialdried over Na2SO4
23. filtrationfiltered
24. customevaporated
25. customto afford a pale pink powder which
26. customwas triturated with ethyl acetate