IP Library › Granted Patent US 8,846,923
Granted Patent B1
US 8,846,923 · App. 14/132,825 · Granted Sep 30, 2014

Preparation of 14-hydroxycodeinone sulfate

Inventors: Zinovy Itov (Cody, WY); Vladimir F. Kuznetsov (Cody, WY); Iouri Voitsekhovski (Cody, WY)
Assignee: Cody Laboratories, Inc.
C07D489/08
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Quick Facts
Patent No.
US 8,846,923
App. No.
14/132,825
Granted
Sep 30, 2014
Kind
B1
Abstract

Synthetic methods are provided for preparation of oxycodone and salts thereof with an improved impurity profile. Thebaine is converted to 14-hydroxycodeinone sulfate intermediate to minimize a 7,8-dihydro-8,14-dihydroxycodeinone impurity. Efficient methods for conversion of oxycodone base to oxycodone hydrochloride are provided to minimize 14-hydroxycodeinone impurity in the final product.

Claims (12)

1. A method for preparation of 14-hydroxycodeinone sulfate or a hydrate thereof comprising

exposing thebaine to hydrogen peroxide or peroxyacid and formic acid in the presence of sodium hydrogen sulfate, sodium sulfate, potassium sulfate, potassium hydrogen sulfate and/or sulfuric acid in an aqueous reaction mixture; and

isolating a precipitate of 14-hydroxycodeinone sulfate or a hydrate thereof from the reaction mixture.

2. The method of claim 1 , wherein the 14-hydroxycodeinone sulfate has less than 0.05%, 0.025%, or 0.01% of a 8,14-dihydroxy-7,8-dihydrocodeinone (DHC) impurity.

3. The method of claim 1 , further comprising purifying the 14-hydroxycodeinone sulfate or hydrate thereof.

4. The method of claim 3 , wherein the purifying comprises recrystallization of the 14-hydroxycodeinone sulfate or hydrate thereof from an aqueous solvent.

5. The method of claim 4 wherein the recrystallized 14-hydroxycodeinone sulfate is selected from 14-hydroxycodeinone hemisulfate, 14-hydroxycodeinone hemisulfate monohydrate, 14-hydroxycodeinone hemisulfate dihydrate, 14-hydroxycodeinone sulfate sesquihydrate, 14-hydroxycodeinone sulfate dihydrate, 14-hydroxycodeinone sulfate monohydrate, 14-hydroxycodeinone sulfate dihydrate, or 14-hydroxycodeinone monosulfate.

6. The method of claim 1 wherein the exposing step is performed in the presence of sodium hydrogen sulfate, sodium sulfate, potassium sulfate, or potassium hydrogen sulfate.

7. The method of claim 1 , wherein the isolated 14-hydroxycodeinone sulfate or hydrate thereof is a 14-hydroxycodeinone hemisulfate or a hydrate thereof.

8. The method of claim 1 , wherein the isolated 14-hydroxycodeinone sulfate or hydrate thereof is selected from a 14-hydroxycodeinone sulfate hemihydrate, monohydrate, sesquihydrate or dihydrate.

9. The method of claim 1 , wherein the isolated 14-hydroxycodeinone sulfate or hydrate thereof exhibits not more than 0.05% total 8,14-dihydroxy-7,8-dihydrocodeinone (DHC) impurity.

10. The method of claim 9 , wherein the isolated 14-hydroxycodeinone sulfate or hydrate thereof exhibits less than 0.01% of an 8,14-dihydroxy-7,8-dihydrocodeinone (DHC) impurity.

Assignments (15)
RELEASE OF SECURITY INTEREST Recorded Jul 15, 2026
From: ALTER DOMUS (US) LLC
To: CODY LABORATORIES, INC.
Reel/Frame 075270/0584 →
RELEASE OF SECURITY INTEREST Recorded Jun 30, 2026
From: WELLS FARGO BANK, NATIONAL ASSOCIATION
To: CODY LABORATORIES, INC.; LANNETT COMPANY, INC.; KREMERS URBAN PHARMACEUTICALS INC.
Reel/Frame 075142/0261 →
RELEASE OF SECURITY INTEREST Recorded Jun 27, 2023
From: ALTER DOMUS (US) LLC
To: LANNETT COMPANY, INC.
Reel/Frame 064088/0641 →
RELEASE OF SECURITY INTEREST Recorded Jun 27, 2023
From: WILMINGTON TRUST, NATIONAL ASSOCIATION
To: LANNETT COMPANY, INC.
Reel/Frame 064088/0663 →
SECURITY INTEREST Recorded Jun 27, 2023
From: LANNETT COMPANY, INC.; CODY LABORATORIES, INC.; KREMERS URBAN PHARMACEUTICALS INC.
To: ALTER DOMUS (US) LLC
Reel/Frame 064088/0709 →
SECURITY INTEREST Recorded Jun 16, 2023
From: CODY LABORATORIES, INC.; LANNETT COMPANY, INC.; KREMERS URBAN PHARMACEUTICALS INC.
To: WELLS FARGO BANK, NATIONAL ASSOCIATION
Reel/Frame 063977/0326 →
TERMINATION AND RELEASE OF INTELLECTUAL PROPERTY SECURITY AGREEMENT Recorded May 2, 2023
From: WELLS FARGO BANK, NATIONAL ASSOCIATION
To: LANNETT HOLDINGS, INC.; CODY LABORATORIES, INC.; LANNETT COMPANY, INC.
Reel/Frame 063516/0192 →
INTELLECTUAL PROPERTY SECURITY AGREEMENT - FIRST LIEN Recorded Apr 23, 2021
From: CODY LABORATORIES, INC.
To: WILMINGTON TRUST, NATIONAL ASSOCIATION
Reel/Frame 056031/0273 →
INTELLECTUAL PROPERTY SECURITY AGREEMENT - 2ND LIEN Recorded Apr 23, 2021
From: CODY LABORATORIES, INC.
To: ALTER DOMUS (US) LLC
Reel/Frame 056031/0521 →
RELEASE OF SECURITY INTEREST IN INTELLECTUAL PROPERTY Recorded Apr 23, 2021
From: ALTER DOMUS (US) LLC (SUCCESSOR TO MORGAN STANLEY SENIOR FUNDING, INC.)
To: KREMERS URBAN PHARMACEUTICALS INC.; CODY LABORATORIES, INC.
Reel/Frame 056031/0185 →
SECURITY INTEREST Recorded Apr 23, 2021
From: CODY LABORATORIES, INC.
To: WILMINGTON TRUST, NATIONAL ASSOCIATION
Reel/Frame 056016/0033 →
SECURITY INTEREST Recorded Dec 7, 2020
From: MORGAN STANLEY SENIOR FUNDING, INC.
To: ALTER DOMUS (US) LLC, AS COLLATERAL AGENT
Reel/Frame 054566/0585 →
INTELLECTUAL PROPERTY SECURITY AGREEMENT Recorded Dec 7, 2020
From: LANNETT HOLDINGS, INC.; CODY LABORATORIES, INC.; LANNETT COMPANY, INC.
To: WELLS FARGO BANK, NATIONAL ASSOCIATION, AS COLLATERAL AGENT
Reel/Frame 054627/0925 →
INTELLECTUAL PROPERTY SECURITY AGREEMENT Recorded Nov 30, 2015
From: CODY LABORATORIES, INC.
To: MORGAN STANLEY SENIOR FUNDING, INC.
Reel/Frame 037171/0921 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 2, 2014
From: ITOV, ZINOVY; KUZNETSOV, VLADIMIR F.; VOITSEKHOVSKI, IOURI
To: CODY LABORATORIES, INC.
Reel/Frame 031911/0488 →