Process for preparing oxymorphone, naltrexone, and buprenorphine

Abstract

Methods are provided which include converting oripavine to other opiates, including converting oripavine to naltrexone, buprenorphine, 14-hydroxymorphinone and/or converting 14-hydroxymorphinone to oxymorphone. Purification and salt formation are optionally included.

1 . A method of purifying oxymorphone comprising:
 obtaining oxymorphone or a salt thereof, and   purifying the oxymorphone or a salt thereof such that the oxymorphone or a salt thereof is substantially free of impurities.   
     
     
         2 . The method of  claim 1 , wherein the purified oxymorphone or a salt thereof is substantially free of alpha-beta-unsaturated ketones. 
     
     
         3 . The method of  claim 1 , comprising adding tartaric acid to a mixture comprising the obtained oxymorphone or salt thereof. 
     
     
         4 . The method of  claim 1 , comprising mixing the obtained oxymorphone or salt thereof with sodium bisulfite. 
     
     
         5 . The method of  claim 1 , wherein the purification is facilitated by a purification aid. 
     
     
         6 . The method of  claim 5 , wherein the purification aid includes an adsorbent, activated carbon, powdered cellulose, tartaric acid, water, or sodium bisulfite. 
     
     
         7 . The method of  claim 1 , wherein the purification comprises heating the oxymorphone or a salt thereof in an acidic medium. 
     
     
         8 . A method of preparing oxymorphone or a salt thereof substantially free of alpha-beta-unsaturated ketones, comprising oxidizing oripavine to obtain 14-hydroxymorphinone. 
     
     
         9 . A method of preparing oxymorphone or a salt thereof substantially free of alpha-beta-unsaturated ketones, comprising reducing 14-hydroxymorphinone to obtain oxymorphone or a salt thereof. 
     
     
         10 . The method of  claim 9 , wherein the 14-hydroxymorphinone is present in a mixture and the mixture is heated in formic acid, and optionally water. 
     
     
         11 . The method of  claim 10 , wherein the mixture is heated in formic acid, water, and optionally alcohol. 
     
     
         12 . The method of  claim 11 , wherein the mixture is heated in formic acid, water, and optionally alcohol, optionally in the presence of a catalyst. 
     
     
         13 . The method of  claim 11 , wherein the mixture is heated in formic acid, water, and optionally alcohol, optionally in the presence of a catalyst and hydrogen. 
     
     
         14 . A method of preparing a purified oxymorphone salt substantially free of alpha-beta-unsaturated ketones, comprising converting oxymorphone to an oxymorphone salt. 
     
     
         15 . The method of  claim 14 , wherein the oxymorphone salt is oxymorphone hydrochloride and meets the specifications in the USP 2006 monograph for oxymorphone hydrochloride. 
     
     
         16 . The method of  claim 14 , wherein the alpha-beta-unsaturated ketones comprise 14-hydroxymorphinone. 
     
     
         17 . The method of  claim 14 , wherein conversion of oxymorphone to an oxymorphone salt comprises preparing the oxymorphone in an alcohol or in a mixture of alcohols. 
     
     
         18 . The method of  claim 14 , wherein conversion of oxymorphone to an oxymorphone salt comprises preparing the oxymorphone in a mixture of water and alcohol. 
     
     
         19 . The method of  claim 17 , wherein the alcohol comprises isopropyl alcohol, methanol, ethanol, propanol, and/or butanol. 
     
     
         20 . The method of  claim 18 , wherein the alcohol comprises isopropyl alcohol, methanol, ethanol, propanol, and/or butanol. 
     
     
         21 . A method for purifying an oxymorphone salt comprising heating the oxymorphone salt in an alcohol or in an alcohol mixture. 
     
     
         22 . The method of  claim 21 , wherein the alcohol is an aqueous alcohol. 
     
     
         23 . The method of  claim 21 , wherein the oxymorphone salt is oxymorphone hydrochloride. 
     
     
         24 . The method of  claim 21 , wherein the alcohol is isopropyl alcohol. 
     
     
         25 . The method of  claim 21 , wherein the oxymorphone salt is dried. 
     
     
         26 . The method of  claim 25 , wherein the oxymorphone salt is dried after heating in the alcohol or alcohol mixture. 
     
     
         27 . A method for preparing a purified oxymorphone or oxymorphone salt substantially free of impurities, comprising
 preparing oxymorphone or an oxymorphone salt in an alcohol, a mixture of alcohol and water, or a mixture of alcohols;   isolating the oxymorphone or oxymorphone salt; and   drying the oxymorphone or oxymorphone salt.   
     
     
         28 . The method of  claim 27 , wherein the preparation of the oxymorphone or oxymorphone salt in an alcohol, a mixture of alcohol and water, or a mixture of alcohols comprises heating the oxymorphone or oxymorphone salt. 
     
     
         29 . The method of  claim 28 , wherein the oxymorphone or oxymorphone salt is heated to 50-60° C. 
     
     
         30 . The method of  claim 28 , wherein the oxymorphone or oxymorphone salt is heated to reflux. 
     
     
         31 . The method of  claim 28 , wherein the oxymorphone or oxymorphone salt is heated in a mixture comprising formic acid, water, and optionally alcohol in the presence of a catalyst. 
     
     
         32 . The method of  claim 28 , wherein the oxymorphone or oxymorphone salt is heated in a mixture comprising formic acid, water, and optionally alcohol, optionally in the presence of a catalyst and hydrogen. 
     
     
         33 . The method of  claim 27 , wherein the alcohol comprises isopropyl alcohol, methanol, ethanol, propanol, and/or butanol. 
     
     
         34 . The method of  claim 27 , wherein the drying comprises applying vacuum and/or heat to the oxymorphone or oxymorphone salt. 
     
     
         35 . A method of preparing oxymorphone or a salt thereof from oripavine, comprising purifying the oxymorphone or the salt thereof such that the oxymorphone or the salt thereof is substantially free of oripavine.