反应详情

温度

52 °C

Sodium pyrimidine-2-carboxylate (154.05 g), imidazole hydrochloride (119.3 g), and 1,1-carbonyldiimidazole (195 g) was slurried in acetonitrile (700 ml). The mixture was warmed from 15° C. to 52° C. over 0.5 h. Carbon dioxide was vigorously evolved between 30 and 50° C. The mixture was stirred 1 h at 52° C. then cooled to 15° C. and N,O-dimethylhydroxylamine hydrochloride (131.90 g) was added with an exotherm to 34° C. The mixture was cooled to 14° C. and methylene chloride (300 ml) and water (500 ml) was added. The pH was adjusted from 7.6 to 1.6 with aqueous sulfuric acid (6.13 M, 226 ml). The phases were separated and the lower aqueous phase washed with methylene chloride (500 ml). To the combined organics was added water (300 ml) and the pH adjusted to 1.18 with aqueous sulfuric acid (6.13 M, 5.1 ml). The phases were separated and the organics washed with saturated aq. sodium bicarbonate (300 ml). All three aqueous phases were serial back extracted with methylene chloride (500 ml). The bicarbonate wash was back extracted with methylene chloride (500 ml). The combined organics were dried (MgSO4) and concentrated in vacuo to a thin slurry. The residue was slurried in methylene chloride (200 ml) and the solids filtered off. The filtrate was concentrated to afford 160.7 g of the title compound as an oil.

1. temperatureThe mixture was warmed from 15° C. to 52° C. over 0.5 h
2. customwas vigorously evolved between 30 and 50° C
3. temperaturethen cooled to 15° C.
4. temperatureThe mixture was cooled to 14° C.
5. customThe phases were separated
6. washthe lower aqueous phase washed with methylene chloride (500 ml)
7. additionTo the combined organics was added water (300 ml)
8. customThe phases were separated
9. washthe organics washed with saturated aq. sodium bicarbonate (300 ml)
10. extractionAll three aqueous phases were serial back extracted with methylene chloride (500 ml)
11. washThe bicarbonate wash
12. extractionwas back extracted with methylene chloride (500 ml)
13. dry with materialThe combined organics were dried (MgSO4)
14. concentrationconcentrated in vacuo to a thin slurry
15. filtrationthe solids filtered off
16. concentrationThe filtrate was concentrated