Hydrogenation process for preparing oxycodone hydrochloride from 14-hydroxycodeinone
View Patent ↗A process for preparing oxycodone hydrochloride, said process comprising hydrogenating 14-hydroxycodeinone in an alcoholic solvent and hydrochloric acid to form oxycodone hydrochloride, wherein (a) the hydrogenation is carried out in the presence of a heterogeneous platinum group metal (PGM) catalyst and hydrogen gas, (b) 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 solution of 14-hydroxycodeinone and hydrochloric acid is heated to temperature before it is exposed to the hydrogen gas, (c) the oxycodone hydrochloride comprises 6a-oxycodol in an amount <about 0.300 area % as determined by HPLC, characterized in that (d) the pH of the solution of 14-hydroxycodeinone and hydrochloric acid is in the range of about ≥2.5 to about ≤4.5; (e) the process is carried out in one pot, and (f) the oxycodone hydrochloride precipitates out of the solution.
1. A process for preparing oxycodone hydrochloride, said process comprising hydrogenating 14-hydroxycodeinone in an alcoholic solvent and hydrochloric acid to form oxycodone hydrochloride, wherein
(a) the hydrogenation is carried out in the presence of a heterogeneous platinum group metal (PGM) hydrogenation catalyst and hydrogen gas,
(b) the hydrogenation is carried out at one or more temperatures greater than ambient temperature, wherein the 14-hydroxycodeinone in an alcoholic solvent and hydrochloric acid is heated to temperature before it is exposed to the hydrogen gas,
(c) the pH of the 14-hydroxycodeinone in an alcoholic solvent and hydrochloric acid is in the range of about ≥2.5 to about ≤4.5,
(d) the process is carried out in one pot; and
(e) the oxycodone hydrochloride comprises 6α-oxycodol in an amount <0.300 area % as determined by HPLC.
2. The process according to claim 1 , wherein the oxycodone hydrochloride substantially precipitates out of solution when the process for preparing oxycodone hydrochloride is carried out in the range of ≥about 30° C. to about ≤about 45° C.
3. The process according to claim 1 , wherein the oxycodone hydrochloride is substantially dissolved when the process is carried out in the range of ≥about 45° C. to about ≤about 85° C.
4. The process according to claim 1 , wherein the alcoholic solvent is selected from the group consisting of methanol, ethanol, n-propanol, and isopropanol or mixtures thereof.
5. The process according to claim 4 , wherein the alcoholic solvent is ethanol.
6. The process according to claim 1 , wherein the hydrogen gas pressure is between about 30-55 psi.
7. The process according to claim 6 , wherein the hydrogen gas pressure is about 40 psi±5 psi.
8. The process according to claim 1 , wherein the one or more temperatures greater than ambient temperature are in the range of ≥about 30° C. to about ≤about 85° C.
9. The process according to claim 8 , wherein the one or more temperatures greater than ambient temperature are in the range of ≥about 30° C. to about ≤50° C.
10. The process according to claim 9 , wherein the one or more temperatures greater than ambient temperature is about 40° C.
11. The process according to claim 1 , wherein the pH is in the range of about ≥3.0 to about ≤4.0.
12. The process according to claim 1 , wherein the heterogeneous platinum group metal hydrogenation catalyst is Pd/C.
13. The process according to claim 1 , wherein the oxycodone hydrochloride comprises 6α-oxycodol in an amount ≤about 0.100 area % as determined by HPLC.
14. The process according to claim 1 , wherein the oxycodone hydrochloride comprises ≤about 25 ppm of an α,β-unsaturated ketone.
15. The process according to claim 14 , wherein the oxycodone hydrochloride comprises ≤about 10 ppm of an α,β-unsaturated ketone.