Process for oseltamivir phosphate

Abstract

The present invention provides an improved and commercially viable process for the preparation of oseltamivir phosphate. Thus, for example, ethyl (3R,4R,5S)-4-amino-5-azido-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylate is acetylated with acetic anhydride in methylene chloride in the presence of triethyl amine in the absence of water to give ethyl (3R,4R,5S)-4-(acetylamino)-5-azido-3-(1-ethylpropoxy)-1-cyclohexene-1-carboxylate.

1 . A process for preparation of the acetyl compound of formula Ill: 
     
       
         
         
             
             
         
       
       which comprises acetylating the amino compound of formula II: 
     
     
       
         
         
             
             
         
       
       with acetic anhydride in an organic solvent in the presence of an organic or inorganic base in the absence of water to give the acetyl compound of formula Ill. 
     
   
   
       2 . The process as claimed in  claim 1 , wherein the organic base used is an organic amine base such as triethyl amine, trimethyl amine, tributyl amine and n-butyl amine; and inorganic base is selected from the group consisting of sodium bicarbonate and potassium bicarbonate. 
   
   
       3 . The process as claimed in  claim 2 , wherein the organic amine base is triethyl amine. 
   
   
       4 . The process as claimed in  claim 2 , wherein the inorganic base is sodium bicarbonate. 
   
   
       5 . The process as claimed in  claim 1 , wherein the acetylation reaction is carried out at about 0-35° C. 
   
   
       6 . The process as claimed in  claim 5 , wherein the reaction is carried out at about 10-30° C. 
   
   
       7 . The process as claimed in  claim 6 , wherein the reaction is carried out at about 15-25° C. 
   
   
       8 . The process as claimed in  claim 1 , wherein the organic solvent is selected from chlorinated hydrocarbon solvents such as methylene chloride, ethylene dichloride and chloroform; hydrocarbon solvents such as n-hexane; and a mixture thereof. 
   
   
       9 . The process as claimed in  claim 8 , wherein the organic solvent is methylene chloride.