Process for the preparation of benzhydrocodone hydrochloride
The invention is directed to processes for the preparation of benzhydrocodone hydrochloride. More particularly, the invention is directed to processes for a one-pot synthesis of benzhydrocodone hydrochloride of improved yield and/or purity.
1. A process for the preparation of benzhydrocodone comprising the steps of:
(a) preparing a first mixture comprising benzoic anhydride, hydrocodone free base, and an organic solvent;
(b) removing a substantial portion of the organic solvent from the first mixture to afford a second mixture; and
(c) heating the second mixture to a temperature in the range of about 100° C. to about 200° C.
2. The process of claim 1 , wherein more than 90% of the organic solvent is removed.
3. The process of claim 1 , wherein more than 95% of the organic solvent is removed.
4. The process of claim 1 , wherein more than 99% of the organic solvent is removed.
5. The process of claim 1 , wherein the organic solvent is selected from the group consisting of toluene, ether, ethyl acetate, and THF.
6. The process of claim 1 , wherein the organic solvent is toluene, and wherein the toluene is removed from the reaction mixture by distillation.
7. The process of claim 6 , wherein the toluene is removed from the reaction mixture under a flow of N 2 gas.
8. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and benzhydrocodone prepared according to the process of claim 1 .
9. The process of claim 1 , further comprising the step of adding to the mixture a first organic solvent and a solvent which is miscible with both the first organic solvent and water.
10. The process of claim 9 , further comprising the step of adding to the mixture an aqueous hydrochloric acid solution.
11. The process of claim 10 , further comprising the step of adjusting the pH of the mixture to a pH in the range of from about pH 1.0 to about pH 5.0.