Process for the preparation of efavirenz

Abstract

A process for the preparation of Efavirenz, (4S)-6-chloro-4-(cyclopropylethynyl)-4-(trifluoromethyl)-1,4-dihydro-2H-3,1-benzoxazin-2-one, of formula (I): comprising reacting the intermediate of formula (II): as a free base or a salt thereof, with diphosgene (TCMCF, trichloromethylchloroformate) Cl 3 CO—COCl in an organic solvent or in a biphasic medium comprised of an organic solvent and water, preferably but not mandatorily in the presence of a weak base in an amount sufficient to neutralize the reaction mixture or in an up to 30% molar excess of such amount.

What is claimed is: 
     
         1 . Intermediate of formula (II) 
       
         
           
           
               
               
           
         
       
       comprising p-chloroaniline in no more than 200 ppm amount, as determined by HPLC. 
     
     
         2 . Efavirenz of formula (I) 
       
         
           
           
               
               
           
         
       
       containing no more than 10 ppm of p-chloroaniline as determined by HPLC.