反应详情

Benzophenone (6.22 g), cyclohexane (22 mL), dried codeine (1.38 g) and chlorotris(triphenylphosphine)rhodium (I) (Wilkinson's catalyst) (0.22 g) were charged into a glass hydrogenation bottle. The bottle was evacuated and filled with hydrogen. The mixture was magnetically agitated at ambient temperature (24–28° C.) while the hydrogen pressure was maintained at 5–15 psi until the pressure drop caused by the hydrogen consumption stopped. A solution of potassium tert-amylate in cyclohexane (12 mL, 15.4% w/w) was charged into the bottle with the reaction mixture in one portion, the mixture was magnetically agitated under nitrogen at ambient temperature for 4 hours and quenched by adding 1.5N acetic acid (13 mL) to the solution with mixing and cooling in an ice bath. Alternatively, in another embodiment the solution may be quenched by adding the solution to 1.5N acetic acid with mixing and cooling in an ice bath. The mixture was filtered, aqueous layer was separated and the organic layer was extracted with 1.5N acetic acid (2 mL). Combined aqueous layer (14.5 mL) according to the assay by HPLC contains 89.7 mg/mL hydrocodone (94% yield), purity 95 area %.

1. customThe bottle was evacuated
2. additionfilled with hydrogen
3. temperaturewas maintained at 5–15 psi until the pressure drop
4. customcaused by the hydrogen consumption
5. additionA solution of potassium tert-amylate in cyclohexane (12 mL, 15.4% w/w) was charged into the bottle with the reaction mixture in one portion
6. stirringthe mixture was magnetically agitated under nitrogen at ambient temperature for 4 hours
7. customquenched
8. additionby adding 1.5N acetic acid (13 mL) to the solution
9. additionwith mixing
10. temperaturecooling in an ice bath
11. customAlternatively, in another embodiment the solution may be quenched
12. additionby adding the solution to 1.5N acetic acid
13. additionwith mixing
14. temperaturecooling in an ice bath
15. filtrationThe mixture was filtered
16. customaqueous layer was separated
17. extractionthe organic layer was extracted with 1.5N acetic acid (2 mL)