Methods for making 3-O-protected morphinones and 3-O-protected morphinone dienol carboxylates

Patent metadata

Field	Value
Publication number	US-9670218-B2
Application number	US-201514637129-A
Country	US
Kind code	B2
Filing date	Mar 3, 2015
Priority date	Feb 6, 2004
Publication date	Jun 6, 2017
Grant date	Jun 6, 2017

Abstract

Disclosed are methods for making aldehydes and ketones comprising allowing the corresponding primary or secondary alcohol to react in the presence of trichoroisocyanuric acid, a compound of formula R 1 SR 2 and a base. In one embodiment, the alcohol is a compound of formula (I):

wherein R 3 is a protecting group.

Also disclosed are methods for making 3-O-protected morphine dienol carboxylates comprising allowing a compound of formula (I) to oxidize in the presence of a chlorine-containing compound and a compound of formula R 1 SR 2 ; and allowing the product of the oxidation step to react with an acylating agent.

First claim

What is claimed is:

1. A method for making a ketone, comprising allowing a secondary alcohol to react in the presence of a compound of formula R 1 SR 2 , trichloroisocyanuric acid, a base, and a solvent selected from aromatic hydrocarbons, (C 1 -C 4 )halogenated hydrocarbons, ethers, glymes, ethyl acetate, and any mixture thereof under conditions sufficient to make the ketone, wherein R 1 and R 2 are each independently —(C 1 -C 20 )alkyl, —(C 3 -C 8 )cycloalkyl, or -phenyl.

2. The method of claim 1 , wherein the amount of base ranges from about 1.0 to about 15.0, from about 2.0 to about 10.0, or from about 2.5 to about 7.0 molar equivalents per molar equivalent of trichloroisocyanuric acid.

3. The method of claim 1 , wherein the base is selected from triethylamine, diisopropylethylamine, pyridine, dimethylpyridine, dimethylaminopyridine, and any mixture thereof and the solvent is selected from benzene, toluene, xylene, mesitylene, chlorobenzene, dichloromethane, chloroform carbon tetrachloride, dichloroethane, diethyl ether, dipropyl ether, di-butyl ether, methyl-tert-butyl ether, tetrahydrofuran, ethylene glycol dimethyl ether, ethyl acetate, and any mixture thereof.

4. The method of claim 3 , wherein the base is triethylamine and the solvent comprises toluene, dichloromethane, or any mixture thereof.

5. The method of claim 3 , wherein the amount of base ranges from about 1.0 to about 15.0, from about 2.0 to about 10.0, or from about 2.5 to about 7.0 molar equivalents per molar equivalent of trichloroisocyanuric acid.

6. The method of claim 1 , wherein R 1 is —CH 3 and R 2 is —(C 1 -C 20 )alkyl.

7. The method of claim 6 , wherein R 1 is —CH 3 and R 2 is —(C 12 )alkyl.

8. The method of claim 7 , wherein the amount of base ranges from about 1.0 to about 15.0, from about 2.0 to about 10.0, or from about 2.5 to about 7.0 molar equivalents per molar equivalent of trichloroisocyanuric acid.

9. The method of claim 7 , wherein the base is selected from triethylamine, diisopropylethylamine, pyridine, dimethylpyridine, dimethylaminopyridine, and any mixture thereof and the solvent is selected from benzene, toluene, xylene, mesitylene, chlorobenzene, dichloromethane, chloroform, carbon tetrachloride, dichloroethane, diethyl ether, dipropyl ether, di-butyl ether, methyl-tert-butyl ether, tetrahydrofuran, ethylene glycol dimethyl ether, ethyl acetate, and any mixture thereof.

10. The method of claim 9 , wherein the base is triethylamine and the solvent comprises toluene dichloromethane or an mixture thereof.

11. The method of claim 9 , wherein the amount of base ranges from about 1.0 to about 15.0, from about 2.0 to about 10.0, or from about 2.5 to about 7.0 molar equivalents per molar equivalent of trichloroisocyanuric acid.

12. The method of claim 7 , wherein the amount of the compound of formula R 1 SR 2 ranges from about 1.0 to about 9.0, from about 2.0 to about 5.0, or from about 2.5 to about 3.5 molar equivalents per molar equivalent of trichloroisocyanuric acid.

13. The method of claim 12 , wherein the amount of base ranges from about 1.0 to about 15.0, from about 2.0 to about 10.0, or from about 2.5 to about 7.0 molar equivalents per molar equivalent of trichloroisocyanuric acid.

14. The method of claim 12 , wherein the base is selected from triethylamine, diisopropylethylamine, pyridine, dimethylpyridine, dimethylaminopyridine, and any mixture thereof and the solvent is selected from benzene, toluene, xylene, mesitylene, chlorobenzene, dichloromethane, chloroform, carbon tetrachloride, dichloroethane, diethyl ether, dipropyl ether, di-butyl ether, methyl-tert-butyl ether, tetrahydrofuran, ethylene glycol dimethyl ether, ethyl acetate, and any mixture thereof.

15. The method of claim 14 , wherein the base is triethylamine and the solvent comprises toluene, dichloromethane, or any mixture thereof.

16. The method of claim 14 , wherein the amount of base ranges from about 1.0 to about 15.0, from about 2.0 to about 10.0, or from about 2.5 to about 7.0 molar equivalents per molar equivalent of trichloroisocyanuric acid.

17. The method of claim 1 , wherein the amount of the compound of formula R 1 SR 2 ranges from about 1.0 to about 9.0, from about 2.0 to about 5.0, or from about 2.5 to about 3.5 molar equivalents per molar equivalent of trichloroisocyanuric acid.

18. The method of claim 17 , wherein the amount of base ranges from about 1.0 to about 15.0, from about 2.0 to about 10.0, or from about 2.5 to about 7.0 molar equivalents per molar equivalent of trichloroisocyanuric acid.

19. The method of claim 17 , wherein the base is selected from triethylamine, diisopropylethylamine, pyridine, dimethylpyridine, dimethylaminopyridine, and any mixture thereof and the solvent is selected from benzene, toluene, xylene, mesitylene, chlorobenzene, dichloromethane, chloroform, carbon tetrachloride, dichloroethane, diethyl ether, dipropyl ether, di-butyl ether, methyl-tert-butyl ether, tetrahydrofuran, ethylene glycol dimethyl ether; ethyl acetate, and any mixture thereof.

20. The method of claim 19 , wherein the base is triethylamine and the solvent comprises toluene, dichloromethane, or any mixture thereof.

21. The method of claim 19 , wherein the amount of base ranges from about 1.0 to about 15.0, from about 2.0 to about 10.0, or from about 2.5 to about 7.0 molar equivalents per molar equivalent of trichloroisocyanuric acid.

22. The method of claim 1 , wherein the secondary alcohol is a straight-chain alkyl secondary alcohol, a straight-chain alkenyl secondary alcohol, a straight-chain alkynyl secondary alcohol, a branch-chain alkyl secondary alcohol, a branch-chain alkenyl secondary alcohol, a branch-chain alkynyl secondary alcohol, a cyclic secondary alcohol, an alkylaryl secondary alcohol, a dialkyl secondary alcohol, an oligomeric secondary alcohol, or a polymeric secondary alcohol.

23. The method of claim 1 , wherein the secondary alcohol is 2-propanol, 2-butanol, 2-pentanol, 3-methylbutan-2-ol, 2-hexanol, 3-methyl-2-pentanol, 4-methyl-2-pentanol, 3-hexanol, 2-methyl-3-pentanol, 2-heptanol, 3-methyl-2-hexanol, 4-methyl-2-hexanol, 5-methyl-2-hexanol, 3-ethyl-2-pentanol, 3,3-dimethyl-2-pentanol, 3,4-dimethyl-2-pentanol, 4,4-dimethyl-2-pentanol, 3-heptanol, 2-methyl-3-heptanol, 4-methyl-3-heptanol, 5-methyl-3-heptanol, 2,2-dimethyl-3-pentanol, 2,4-dimethyl-3-pentanol, 2-ethyl-3-pentanol, 4-ethyl-3-pentanol, 4-heptanol, cyclohexanol, 1-phenyl-1-ethanol, 1-phenyl-1-propanol, diphenylmethanol, an oligomer of polyvinylalcohol, or polyvinylalcohol.

24. The method of claim 1 , wherein the amount of secondary alcohol ranges from about 1.0 to about 9.0, from about 2.0 to about 5.0, or from about 2.0 to about 4.0 molar equivalents per molar equivalent of trichloroisocyanuric acid.

Assignees

• Purdue Pharma Lp

Inventors

• Stumpf Andreas

Classifications

• A61P25/04

  Centrally acting analgesics, e.g. opioids · CPC title

• C07D491/22

  in which the condensed system contains four or more hetero rings · CPC title

• C07F7/1804

  Compounds having Si-O-C linkages (Si-O-acyl linkages C07F7/1896) · CPC title

• C07D489/02 Primary

  with oxygen atoms attached in positions 3 and 6, e.g. morphine, morphinone · CPC title

• Y02P20/55

  Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups · CPC title