Process for improved oxymorphone synthesis
Processes for preparing oxymorphone are provided. Said processes encompass a step which is a hydrogenation of an 14-hydroxymorphinone salt in the presence of trifluoroacetic acid and/or a glycol.
1. A process for preparing oxymorphone or a salt or solvate thereof from a 14-hydroxymorphinone salt or a solvate thereof
the process comprising the steps of
(a) providing a solution or suspension of the 14-hydroxymorphinone salt or a solvate thereof;
(b) adding trifluoroacetic acid and/or a glycol; and
(c) reducing the 14-hydroxymorphinone present in the solution or suspension to the oxymorphone by hydrogenation,
wherein
X n− is an anion selected from the group consisting of Cl − , HSO 4 − , SO 4 2− , methanesulfonate, tosylate, trifluoroacetate, H 2 PO 4 − , HPO 4 2− , PO 4 3− , oxalate, perchlorate, and any mixtures thereof; and
n is 1,2, or 3.
2. The process of claim 1 , wherein trifluoroacetic acid and the glycol are added in step (b).
3. The process of claim 1 , wherein n is 2 and X n− is SO 4 2− .
4. The process of claim 1 , wherein the amount of trifluoroacetic acid is 99 mol % or less as compared to the molar amount of 14-hydroxymorphinone contained in the 14-hydroxymorphinone salt.
5. The process of claim 4 , wherein the amount of trifluoroacetic acid is from 30 mol % to 50 mol % as compared to the molar amount of 14-hydroxymorphinone contained in the 14-hydroxymorphinone salt.
6. The process of claim 1 , wherein the glycol is selected from the group consisting of ethylene glycol, propylene glycol, 1,3-propanediol, 1,2-butanediol, 1,3-butanediol, neopentylglycol, and mixtures thereof.
7. The process of claim 6 , wherein the glycol is ethylene glycol, propylene glycol, or a mixture thereof.
8. The process of claim 1 , wherein the glycol added in step (b) is in the range of from 1 to 8 volumes/weight calculated from the glycol volume in mL in relation to the weight in grams of the 14-hydroxymorphinone salt.
9. The process of claim 1 , wherein the hydrogenation in step (c) is performed with H 2 and a hydrogenation catalyst.
10. The process of claim 1 , wherein a mixture of water and the glycol is used as solvent, wherein the mixture is in a range from 20:80 to 45:55 glycol:water.
11. The process of claim 1 , additionally comprising the step:
(d) adding a base, thus raising the pH to a pH where the oxymorphone precipitates as its free base, and isolating the oxymorphone as its free base or a solvate thereof.
12. The process of claim 11 , wherein the base added in step (d) is NaOH.