# US 9,040,726 B2 · Process for the preparation of quaternary N-alkyl morphinan alkaloid salts

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- Number: US 9,040,726 B2
- Document ID: US9040726B2
- Status: Granted
- Kind: B2
- Application number: 12/553,144
- Filed: 2009-09-03
- Published: 2010-02-11
- Granted: 2015-05-26
- Earliest claimed: 2009-09-03
- Assignees: Mallinckrodt Inc.
- Applicants: Peter X. Wang; Gary L. Cantrell; Robert E. Halvachs; Kevin R. Roesch; Henry J. Buehler; Joseph P. Haar
- Inventors: Peter X. Wang; Gary L. Cantrell; Robert E. Halvachs; Kevin R. Roesch; Henry J. Buehler; Joseph P. Haar
- Web page: https://patentgrep.com/patent/US9040726B2

## CPC

- A61K 31/485: Morphinan derivatives, e.g. morphine, codeine
- A61P 25/04: Centrally acting analgesics, e.g. opioids
- C07D 489/02: with oxygen atoms attached in positions 3 and 6, e.g. morphine, morphinone
- Y02P 20/582: Recycling of unreacted starting or intermediate materials
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- Y02P: CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS

## Abstract

An improved process for the N-alkylation of tertiary morphinan alkaloid bases to form the corresponding quaternary morphinan alkaloid derivatives.

## Claims

### Claim 1

A composition comprising R-naltrexone methobromide, S-naltrexone methobromide, the C(3)-O-methyl derivative of naltrexone methobromide, and naltrexone wherein the composition contains at least 70% (w/w) of R-naltrexone methobromide, at least 1% of S-naltrexone methobromide, but no more than 0.2% (w/w) of the C(3)-O-methyl derivative of naltrexone methobromide, based upon the combined weight of the R-naltrexone methobromide, S-naltrexone methobromide, C(3)-O-methyl derivative of naltrexone methobromide, and naltrexone in the composition.

### Claim 2 (depends on 1)

The composition of claim 1, the composition being in the form of a mixture with the weight ratio of S-naltrexone methobromide to C(3)-O-methyl derivative of naltrexone methobromide in the mixture being at least 10:1.

### Claim 3 (depends on 2)

The composition of claim 2, wherein the mixture is in the form of a slurry or a solution.

### Claim 4 (depends on 1)

The composition of claim 1, the composition being in the form of a mixture with the weight ratio of naltrexone to C(3)-O-methyl derivative of naltrexone methobromide in the mixture being at least 10:1.

### Claim 5 (depends on 4)

The composition of claim 4, wherein the mixture is in the form of a slurry or a solution.

### Claim 6 (depends on 2)

The composition of claim 2, wherein the composition contains no more than 0.1% (w/w) of the C(3)-O-methyl derivative of naltrexone methobromide, based upon the combined weight of the R-naltrexone methobromide, S-naltrexone methobromide, C(3)-O-methyl derivative of naltrexone methobromide, and naltrexone in the composition.

### Claim 7 (depends on 1)

The composition of claim 1, the composition being in the form of a crystallized solid with the weight ratio of S-naltrexone methobromide to C(3)-O-methyl derivative of naltrexone methobromide in the crystallized solid being at least 10:1.

### Claim 8 (depends on 1)

The composition of claim 1, the composition being in the form of a crystallized solid with the weight ratio of naltrexone to C(3)-O-methyl derivative of naltrexone methobromide in the crystallized solid being at least 10:1.

### Claim 9 (depends on 7)

The composition of claim 7, wherein the composition contains no more than 0.1% (w/w) of the C(3)-O-methyl derivative of naltrexone methobromide, based upon the combined weight of the R-naltrexone methobromide, S-naltrexone methobromide, C(3)-O-methyl derivative of naltrexone methobromide, and naltrexone in the composition.