Process for the preparation of oxymorphone alkaloid and oxymorphone salts
View Patent ↗The present invention provides a process for preparing an oxymorphone acid adduct, said process comprising hydrogenating an aqueous solution of 14-hydroxymorphinone and an acid to form a solution of the oxymorphone acid adduct, wherein the hydrogenation is carried out at one or more temperatures greater than 40° C. in the presence of a hydrogenation catalyst and hydrogen gas, wherein the level of 6α-oxymorphol produced is ≦3.00 area % as determined by HPLC.
1. A process for preparing an oxymorphone acid adduct, said process comprising hydrogenating an aqueous solution of 14-hydroxymorphinone and an acid to form a solution of the oxymorphone acid adduct, wherein the hydrogenation is carried out at one or more temperatures greater than 40° C. in the presence of a hydrogenation catalyst and hydrogen gas, wherein the aqueous solution is heated to temperature before being exposed to the hydrogen gas, and wherein the solution of oxymorphone acid adduct comprises 6α-oxymorphol in an amount ≦3.00 area % as determined by HPLC.
2. A process according to claim 1 , wherein the acid is selected from the group consisting of acetic acid, phosphoric acid, citric acid, tartaric acid, oxalic acid, hydrochloric acid, hydrobromic acid and a mixture thereof.
3. A process according to claim 1 , wherein the hydrogenation is carried out at one or more temperatures in the range of about ≧50° C. to about ≦100° C.
4. A process according to claim 3 , wherein the hydrogenation is carried out at one or more temperatures in the range of ≧about 50° C. to about ≦85° C.
5. A process according to claim 1 , wherein the hydrogenation catalyst is a heterogeneous or homogenous catalyst, preferably a heterogeneous catalyst.
6. A process according to claim 5 , wherein the heterogeneous catalyst is a heterogeneous platinum group metal (PGM) catalyst, preferably a heterogeneous palladium catalyst.
7. A process according to claim 1 , wherein the solution of oxymorphone acid adduct comprises 6α-oxymorphol in an amount ≦about 1.10 area % as determined by HPLC.
8. A process according to claim 1 , wherein the process further comprises treating the solution of oxymorphone acid adduct to form solid oxymorphone acid adduct.
9. A process according to claim 8 , wherein the process further comprises treating the solid oxymorphone acid adduct to form oxymorphone alkaloid.
10. A process according to claim 1 , wherein the process further comprises treating the solution of oxymorphone acid adduct with a base to form oxymorphone alkaloid.
11. A process according to claim 9 , wherein the oxymorphone alkaloid comprises 6α-oxymorphol in an amount ≦about 1.10 area % as determined by HPLC.
12. A process according to claim 10 , wherein the oxymorphone alkaloid comprises 6α-oxymorphol in an amount ≦about 1.10 area % as determined by HPLC.
13. A process according to claim 9 , wherein the oxymorphone alkaloid comprises ≦about 50 ppm of an α,β-unsaturated ketone.
14. A process according to claim 10 , wherein the oxymorphone alkaloid comprises ≦about 50 ppm of an α,β-unsaturated ketone.
15. A process according to claim 11 , wherein the oxymorphone alkaloid comprises ≦about 50 ppm of an α,β-unsaturated ketone.
16. A process according to claim 12 , wherein the oxymorphone alkaloid comprises ≦about 50 ppm of an α,β-unsaturated ketone.
17. A process according to claim 1 , wherein the oxymorphone acid adduct comprises ≦about 50 ppm of an α,β-unsaturated ketone.
18. A process according to claim 8 , wherein the oxymorphone acid adduct comprises ≦about 50 ppm of an α,β-unsaturated ketone.
19. A process for preparing an oxymorphone acid adduct, said process comprising hydrogenating an aqueous solution of 14-hydroxymorphinone and an acid to form a solution of the oxymorphone acid adduct, wherein the hydrogenation is carried out at one or more temperatures greater than 40° C. in the presence of a hydrogenation catalyst and hydrogen gas, wherein the aqueous solution is heated to temperature before being exposed to the hydrogen gas, and wherein the solution of the oxymorphone acid adduct comprises less 6α-oxymorphol than that produced on carrying out the hydrogenation at 40° C. or less.
20. A process for preparing an oxymorphone acid adduct, said process comprising hydrogenating 14-hydroxymorphinone and an acid in a solvent comprising an alcohol and optionally water to form the oxymorphone acid adduct, wherein the hydrogenation is carried out at one or more temperatures greater than ambient temperature in the presence of a hydrogenation catalyst and hydrogen gas, wherein the 14-hydroxymorphinone, acid and solvent are heated to temperature before being exposed to the hydrogen gas, and wherein the oxymorphone acid adduct comprises less 6α-oxymorphol than that produced on carrying out the hydrogenation at ambient temperature.