反应详情

温度

81 °C

Morphine base (30.0 g, wet, 75% wt, 78.85 mmol) was dried in a vacuum oven at 90° C. for 3 h. The dried solid was added to a reaction flask, along with water (30 mL) and EtOH (60 mL). The reaction mixture was stirred to form a suspension. The reactor was flushed with nitrogen and the reaction mixture was kept under nitrogen throughout the reaction. The reaction flask was charged with H2SO4 (98%, 7.73 g, 78.85 mmol) and the catalyst (RuCl3.xH2O, 0.20 g). The reaction mixture was heated to reflux (80-82° C.) for 16 h. HPLC analysis indicated that 96.8% (area) hydromorphone was formed. The reaction mixture was cooled down overnight. Acetonitrile (30 mL) was added to the reaction mixture and the mixture was heated at reflux for 1 h. The pH of the reaction mixture was adjusted the pH to 1.6 with 50% NaOH. EtOH (90 mL) was added to the mixture, which as cooled down to 15° C. for 1 h. The mixture was filtered, and the solid was washed with 95% EtOH (2×15 mL). The solid was dried under vacuum at 65° C. for 18 h to give 11.6 g of hydromorphone sulfate as solids (purity>99% area).

1. dry with materialMorphine base (30.0 g, wet, 75% wt, 78.85 mmol) was dried in a vacuum oven at 90° C. for 3 h
2. additionThe dried solid was added to a reaction flask, along with water (30 mL) and EtOH (60 mL)
3. customto form a suspension
4. customThe reactor was flushed with nitrogen
5. customthe reaction mixture was kept under nitrogen throughout the reaction
6. temperatureThe reaction mixture was heated
7. customwas formed
8. temperatureThe reaction mixture was cooled down overnight
9. temperaturethe mixture was heated
10. temperatureat reflux for 1 h
11. temperatureas cooled down to 15° C. for 1 h
12. filtrationThe mixture was filtered
13. washthe solid was washed with 95% EtOH (2×15 mL)
14. customThe solid was dried under vacuum at 65° C. for 18 h