反应详情

温度

35 °C

HOAc (30 mL) and water (120 mL) were added to a 250 mL flask (pH=2.6, ˜150 mL). With the agitator on, oripavine (30.00 g, assayed to be 96% wt/wt, containing oripavine 97 mmol) was charged to the flask (final pH=3.66). Heat was released and the final solution reached 25° C. from 20° C., pH=3.66. The reaction mixture was cooled to 5° C. to 10° C., and, CH3CO3H (23.4 g, containing 33% wt/wt peroxyacetic acid and 5.34% H2O2 containing 97 mmol peracetic acid) was added over 10 minutes. Heat was released during the addition and the reaction temperature was maintained below 15° C. (primarily 10° C. to 15° C.) during the addition by ice water bath. The cooling bath was removed after the addition was completed. The temperature of the reaction mixture was 10° C. at this point. The reaction mixture was stirred for another 30 minutes after cooling bath was removed and the final temperature reached 15° C. Ascorbic acid (1.5 g) was added to the reaction mixture. The solution was heated to 35° C. over a 30 minute period and maintained at 35° C. for 1 hour afterwards. The reaction mixture was transferred to a pressure bearing flask (350 mL) for the reduction reaction. The flask for the oxidation was washed with the 2% HOAc (v/v; 2×7.5 mL). The washes were transferred to the reduction flask. 1.0 g of 10% Pd/C was added and the flask was pump/purged first with nitrogen and then with hydrogen each 4 times. The flask was cycled under vacuum and hydrogen 4 times. The reaction mixture was stirred under hydrogen (60 PSI) at 85° C. to 90° C. (90° C. oil bath) for 4.5 hours. The reaction mixture was cooled down to 35° C. and filtered. The recovered solid was washed with a solution of 2% HOAc/H2O (v/v, 3×15 mL). Yield of oxymorphone formed in the solution was calculated by HPLC analysis: 95%.

1. temperatureHeat
2. customreached 25° C. from 20° C.
3. temperatureThe reaction mixture was cooled to 5° C. to 10° C.
4. additionwas added over 10 minutes
5. temperatureHeat
6. additionwas released during the addition
7. temperaturethe reaction temperature was maintained below 15° C. (primarily 10° C. to 15° C.)
8. additionduring the addition by ice water bath
9. customThe cooling bath was removed
10. additionafter the addition
11. customwas 10° C. at this point
12. temperatureafter cooling bath
13. customwas removed
14. customreached 15° C
15. additionAscorbic acid (1.5 g) was added to the reaction mixture
16. temperaturemaintained at 35° C. for 1 hour afterwards
17. customThe reaction mixture was transferred to a pressure bearing flask
18. custom(350 mL) for the reduction reaction
19. washThe flask for the oxidation was washed with the 2% HOAc (v/v; 2×7.5 mL)
20. addition1.0 g of 10% Pd/C was added
21. customthe flask was pump/purged first with nitrogen
22. stirringThe reaction mixture was stirred under hydrogen (60 PSI) at 85° C. to 90° C. (90° C. oil bath) for 4.5 hours
23. temperatureThe reaction mixture was cooled down to 35° C.
24. filtrationfiltered
25. washThe recovered solid was washed with a solution of 2% HOAc/H2O (v/v, 3×15 mL)