Preparation of oxycodone

Abstract

A method of purifying oxycodone or a salt thereof includes the steps of: a) preparing a solution including the oxycodone or salt thereof in a solvent, the solution having a pH less than 6, and; b) maintaining the solution at a temperature of at least 55° C. for a period of at least 1 hour; wherein the step of maintaining is performed in the absence of hydrogenation reagents.

1 . A method of purifying oxycodone or a salt thereof, comprising the steps of:
 a) preparing a solution comprising the oxycodone or salt thereof in a solvent, said solution having a pH less than 6, and;   b) maintaining the solution at a temperature of at least 55° C. for a period of at least 3 hours;   
     wherein the step of maintaining is performed in the absence of hydrogenation reagents. 
   
   
       2 . The method of  claim 1 , wherein the oxycodone or salt thereof comprises oxycodone hydrochloride. 
   
   
       3 . The method of  claim 1 , wherein the pH is less than 5. 
   
   
       4 . The method of  claim 1 , wherein the pH is less than 3. 
   
   
       5 . The method of  claim 1 , wherein the temperature is at least 60° C. 
   
   
       6 . The method of  claim 1 , wherein the temperature is from about 70° C. to 75° C. 
   
   
       7 . The method of  claim 1 , wherein the period is at least 5 hours. 
   
   
       8 . The method of  claim 1 , wherein the period is from 5 to 10 hours. 
   
   
       9 . The method of  claim 1 , further comprising after step (b) the steps of:
 c) contacting the solution with hydrogenation reagents for a period of at least 1 hour; and   d) crystallizing the product of step (c) to form the purified oxycodone or salt thereof.   
   
   
       10 . The method of  claim 9 , wherein the purified oxycodone or salt thereof is oxycodone hydrochloride. 
   
   
       11 . The method of  claim 9 , wherein the hydrogenation reagents comprise a hydrogenation catalyst and either hydrogen or a hydrogen transfer reagent. 
   
   
       12 . The method of  claim 1 , wherein the pH is less than or about 1. 
   
   
       13 . The method of  claim 9 , wherein the pH is less than or about 1. 
   
   
       14 . The method of  claim 9 , wherein the purified oxycodone or salt thereof comprises about 3 ppm of 14-hydroxycodeinone. 
   
   
       15 . The method of  claim 9 , wherein the purified oxycodone or salt thereof comprises about 0 ppm of 14-hydroxycodeinone. 
   
   
       16 . The method of  claim 1 , further comprising, prior to preparing the solution, the steps of washing 14-hydroxycodeinone with ethanol and subsequently converting the 14-hydroxycodeinone to a crude oxycodone, wherein the crude oxycodone is the oxycodone or oxycodone salt that is used for preparing the solution. 
   
   
       17 . The method of  claim 1 , further comprising, prior to preparing the solution, the step of washing oxycodone with ethanol to form washed oxycodone and optionally forming a salt therefrom, wherein the washed oxycodone or salt formed therefrom is the oxycodone or oxycodone salt that is used to prepare the solution. 
   
   
       18 . The method of  claim 17 , further comprising, prior to the step of washing the oxycodone, the steps of washing 14-hydroxycodeinone with ethanol and subsequently converting the 14-hydroxycodeinone to a crude oxycodone, wherein the crude oxycodone is the oxycodone that is washed with ethanol. 
   
   
       19 . The method of  claim 18 , further comprising after step (b) the steps of:
 c) contacting the solution with hydrogenation reagents for a period of at least 1 hour; and   d) crystallizing the product of step (c) to form the purified oxycodone or salt thereof;   wherein the purified oxycodone or salt thereof is oxycodone hydrochloride, the pH is less than or about 1, and step (b) is carried out for at least 5 hours at a temperature from about 70° C. to 75° C.   
   
   
       20 . The method of  claim 19 , wherein step (c) is carried out for about 6 hours at a temperature from about 45° C. to 55° C. 
   
   
       21 . The method of  claim 19 , wherein step (b) is carried out for about 10 hours at a temperature of about 75° C. 
   
   
       22 . The method of  claim 11  further comprising, after step (c), removing the hydrogenation catalysts by filtering to provide the product which is crystallized in step (d). 
   
   
       23 . The method of  claim 1 , further comprising after step (b) the steps of:
 c) contacting the solution with hydrogenation reagents for a period of at least 1 hour; and   d) crystallizing the product of step (c) to form the purified oxycodone or salt thereof;   wherein the purified oxycodone or salt thereof is oxycodone hydrochloride, the pH is less than or about 1, and step (b) is carried out for at least 5 hours at a temperature from about 70° C. to 75° C.   
   
   
       24 . The method of  claim 23 , wherein step (c) is carried out for about 6 hours at a temperature from about 45° C. to 55° C. 
   
   
       25 . The method of  claim 23 , wherein step (b) is carried out for about 10 hours at a temperature of about 75° C.