反应详情

温度

97.5 °C

A mixture of 4,5α-Epoxy-3,14-dihydroxy-17-methyl morphinan-6-one (32.0 kg), toluene (225 L) and acetic acetic anhydride (32 L) were heated to 95-100° C. and maintained for 8.0 hrs. After reaction completion, the solvent was distilled at 60-65° C. under vacuum and acetic anhydride traces were stripped out with toluene and the residue degassed. Chlorobenzene (290 L), lithium carbonate (23.5 kg), sodium iodide (20.8 kg), DM water (3.2 L) and ethylchloroformate (280 L) were added to the degassed mass and heated to 95-105° C., the reaction was maintained at 95-105° C. for 12.0 hrs. After reaction completion, the solids were filtered and filtrate was concentrated at 70° C. under vacuum and the residue degassed. To the degassed mass acetic acid (96 L) and 15% aqueous sulphuric acid (480 L) was added and the solution was heated to 100-110° C. and maintained at 100-110° C. for 24 hrs. After reaction completion, the reaction mass was cooled to 0-5° C. and pH of the solution was adjusted to ˜4.0 with aqueous ammonia. The aquesous solution was washed with MDC and the aqueous layer was separated. The separated aqueous layer was treated with activated charcoal and filtered. The pH of the filtrate was adjusted to 9-9.5 with aqueous ammonia at below 20° C., the solution was further cooled to 0-5° C. and the product formed was filtered and dried. Yield: 20.3 kg.

1. temperaturemaintained for 8.0 hrs
2. customAfter reaction completion
3. distillationthe solvent was distilled at 60-65° C. under vacuum and acetic anhydride traces
4. customthe residue degassed
5. additionChlorobenzene (290 L), lithium carbonate (23.5 kg), sodium iodide (20.8 kg), DM water (3.2 L) and ethylchloroformate (280 L) were added to the degassed mass
6. temperatureheated to 95-105° C.
7. temperaturethe reaction was maintained at 95-105° C. for 12.0 hrs
8. customAfter reaction completion
9. filtrationthe solids were filtered
10. concentrationfiltrate was concentrated at 70° C. under vacuum
11. customthe residue degassed
12. additionTo the degassed mass acetic acid (96 L) and 15% aqueous sulphuric acid (480 L) was added
13. temperaturethe solution was heated to 100-110° C.
14. temperaturemaintained at 100-110° C. for 24 hrs
15. customAfter reaction completion
16. temperaturethe reaction mass was cooled to 0-5° C.
17. washThe aquesous solution was washed with MDC
18. customthe aqueous layer was separated
19. additionThe separated aqueous layer was treated with activated charcoal
20. filtrationfiltered
21. customwas adjusted to 9-9.5 with aqueous ammonia at below 20° C.
22. temperaturethe solution was further cooled to 0-5° C.
23. customthe product formed
24. filtrationwas filtered
25. customdried