IP Library › Granted Patent US 9,233,972
Granted Patent B2
US 9,233,972 · App. 14/459,983 · Granted Jan 12, 2016

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
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 9,233,972
App. No.
14/459,983
Granted
Jan 12, 2016
Kind
B2
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 (13)

1. A method for preparation of isolated 14-hydroxycodeinone hemisulfate dihydrate comprising

exposing thebaine to hydrogen peroxide or peroxyacid, and another organic acid, in the presence of sodium hydrogen sulfate, sodium sulfate, potassium sulfate, and/or potassium hydrogen sulfate 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 another organic acid is formic acid.

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

4. The method of claim 1 , further comprising purifying the 14-hydroxycodeinone hemisulfate dihydrate.

5. The method of claim 4 , wherein the purifying comprises recrystallization of the 14-hydroxycodeinone hemisulfate dihydrate from an aqueous solvent.

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

7. The method of claim 1 , wherein the exposing step comprises adding the hydrogen peroxide or peroxyacid to the thebaine, and the another organic acid in the presence of sodium hydrogen sulfate, sodium sulfate, potassium sulfate, and/or potassium hydrogen sulfate in the aqueous reaction mixture.

8. The method of claim 7 , wherein the thebaine is exposed to hydrogen peroxide or peroxyacid and another organic acid in the presence of sodium hydrogen sulfate and/or potassium hydrogen sulfate in the aqueous reaction mixture.

9. The method of claim 8 , wherein the 14-hydroxycodeinone hemisulfate dihydrate has less than 0.05% of total DHC impurity.

10. The method of claim 8 , wherein the 14-hydroxycodeinone hemisulfate dihydrate has less than 0.025% of total DHC impurity.

11. The method of claim 8 , wherein the 14-hydroxycodeinone hemisulfate dihydrate has less than 0.01% of total DHC impurity.

Assignments (14)
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 →
SECURITY INTEREST Recorded Apr 23, 2021
From: CODY LABORATORIES, INC.
To: WILMINGTON TRUST, NATIONAL ASSOCIATION
Reel/Frame 056016/0033 →
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 →
INTELLECTUAL PROPERTY SECURITY AGREEMENT - 2ND LIEN Recorded Apr 23, 2021
From: CODY LABORATORIES, INC.
To: ALTER DOMUS (US) LLC
Reel/Frame 056031/0521 →
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 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 →
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 Nov 30, 2015
From: CODY LABORATORIES, INC.
To: MORGAN STANLEY SENIOR FUNDING, INC.
Reel/Frame 037171/0921 →
Continuity (2)
Continuation 14132825 · Dec 18, 2013
Related Publication 20150166554A1 · Jun 18, 2015