# US 2017/0253604 A9 · Process for improved oxymorphone synthesis

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- Number: US 2017/0253604 A9
- Document ID: US20170253604A9
- Status: Published application
- Kind: A9
- Application number: 15/110,824
- Filed: 2015-01-15
- Published: 2017-09-07
- Earliest claimed: 2014-01-15
- Assignees: Rhodes Technologies
- Applicants: Rhodes Technologies
- Inventors: Joshua Robert GIGUERE; Keith Edward MCCARTHY; Marcel SCHLEUSNER
- Web page: https://patentgrep.com/patent/US20170253604A9

## CPC

- C07D 489/02: with oxygen atoms attached in positions 3 and 6, e.g. morphine, morphinone
- A61P 25/04: Centrally acting analgesics, e.g. opioids
- C07D 489/08: Oxygen atom
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS

## Abstract

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.

## Claims

### Claim 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) hydrogenating the resulting mixture, to reduce the 14-hydroxymorphinone to the oxymorphone,
wherein
Xn− is an anion selected from the group consisting of Cl−, HSO4−, SO42−, methanesulfonate, tosylate, trifluoroacetate, H2PO4−, HPO42−, PO43−, oxalate, perchlorate, and any mixtures thereof; and
n is 1,2, or 3.

### Claim 2 (depends on 1)

The process of claim 1, wherein trifluoroacetic acid and the glycol are added in step (b).

### Claim 3 (depends on 1)

The process of claim 1, wherein n is 2 and Xn− is SO42−.

### Claim 4 (depends on 1)

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.

### Claim 5 (depends on 4)

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.

### Claim 6 (depends on 1)

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.

### Claim 7 (depends on 6)

The process of claim 6, wherein the glycol is ethylene glycol, propylene glycol, or a mixture thereof.

### Claim 8 (depends on 1)

The process of claim 1, wherein the glycol added in step (b) is in the range of 1 to 8 volumes in mL in relation to the weight in grams of the 14-hydroxymorphinone salt.

### Claim 9 (depends on 1)

The process of claim 1, wherein the hydrogenation in step (c) is performed with H2 and a hydrogenation catalyst.

### Claim 10 (depends on 1)

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.

### Claim 11 (depends on 1)

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.

### Claim 12 (depends on 11)

The process of claim 11, wherein the base added in step (d) is NaOH.

### Claim 13 (depends on 1)

A process for preparing oxymorphone or a salt or solvate thereof from oripavine, the process comprising of the steps
(aa) oxidizing the oripavine to 14-hydroxymorphinone;
(bb) adding an acid H+nXn− to the reaction mixture before, during and/or after the oxidation reaction;
(cc) optionally precipitating the resulting 14-hydroxymorphinone as 14-hydroxyrmorphinone salt or a solvate thereof;
(dd) optionally isolating the precipitated14-hydroxymorphinone salt or solvate thereof; and
(ee) performing the process according to claim 1, and optionally 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;
wherein
Xn− is an anion selected from the group consisting of Cl−, HSO4−, SO42−, methanesulfonate, tosylate, trifluoroacetate, H2PO4−, HPO42−, PO43−, oxalate, perchlorate, and any mixtures thereof; and
n is 1, 2, or 3.

### Claim 14 (depends on 1)

Oxymorphone prepared by the process of claim 1.

### Claim 15 (depends on 14)

The oxymorphone of claim 14, which contains less than 1 ppm 8-hydroxyoxymorphone and less than 1 ppm 14-hydroxymorphinone.

### Claim 16 (depends on 13)

The process of claim 13, additionally comprising the step of adding the 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.

### Claim 17 (depends on 13)

Oxymorphone prepared by the process of claim 13.

### Claim 18 (depends on 17)

The oxymorphone of claim 17, which contains less than 1 ppm 8-hydroxyoxymorphone and less than 1 ppm 14-hydroxymorphinone.