Methods of producing molindone and its salts
View Patent ↗The present invention is directed towards novel methods of synthesis of molindone, synthesis of the intermediates of molindone, and high-purity compositions of molindone. In particular, the invention relates to the methods of synthesis of molindone through the Mannich reaction.
1. A process for preparing 2,3-pentanedione-2-oxime (SUMO-1), having the following structure:
comprising reacting 2,3-pentanedione having the following structure:
with hydroxylamine hydrochloride in the presence of a base;
wherein the reaction is carried out at a temperature of between −10° C. to 20° C. and at pH values ranging from 4.5 to 9.5.
2. The process of claim 1 , wherein the base is selected from the group consisting of lithium hydroxide (LiOH), sodium hydroxide (NaOH), potassium hydroxide (KOH), lithium carbonate (Li 2 CO 3 ), potassium carbonate (K 2 CO 3 ), sodium carbonate (Na 2 CO 3 ), and combinations thereof.
3. The process of claim 1 , wherein one to three equivalents of the base are used in the reaction.
4. The process of claim 1 , wherein the base is sodium carbonate.
5. The process of claim 4 , wherein one to three equivalents of sodium carbonate are used in the reaction.
6. The process of claim 5 , wherein one equivalent of sodium carbonate are used in the reaction.
7. The process of claim 5 , wherein 1.1 equivalent of sodium carbonate are used in the reaction.
8. The process of claim 5 , wherein 1.2 equivalent of sodium carbonate are used in the reaction.
9. The process of claim 1 , wherein the reaction is carried out at a temperature of from 5° C. to 20° C.
10. The process of claim 1 , wherein the reaction is carried out at a temperature of from 5° C. to 0° C.
11. The process of claim 1 , wherein the reaction is carried out at a temperature of from 0° C. to −15° C.
12. The process of claim 1 , wherein the reaction is carried out at a temperature of from −5° C. to −10° C.
13. The process of claim 1 , wherein the reaction is carried out at pH values ranging from 4.5 to 8.
14. The process of claim 1 , wherein the reaction is carried out at pH values ranging from 8 to 9.5.
15. The process of claim 1 , carried out in the presence of a solvent selected from the group consisting of water, methyl tertiary butyl ether (MTBE), methanol, ethanol, isopropanol, tetrahydrofuran (THF), acetonitrile, pyridine, ethyl ether, acetic acid and combinations thereof.
16. The process of claim 15 , further comprising adding a solvent selected from the group consisting of glycerol, ethylene glycol, propylene glycol, diethylene glycol and combinations thereof.
17. The process of claim 1 , further comprising adding an anti-freezing agent selected from the alkali and alkaline earth metal halides.
18. The process of claim 17 , wherein the anti-freezing agent is selected from the group consisting of sodium chloride (NaCl), potassium chloride (KCl), calcium chloride (CaCl 2 ), magnesium chloride (MgCl 2 ), and combinations thereof.
19. The process of claim 1 , wherein the ratio of SUMO-1 to SUMO-1 isomer is greater than 5.
20. The process of claim 1 , having less than 0.2% of 2,3-pentadione-2,3-dioxime impurities.