Preparation of paroxetine involving novel intermediates

Abstract

Disclosed are processes for preparing novel carbamate intermediates of paroxetine comprising dealkylating N-alkylparoxetine by reaction thereof with a haloalkyl ester of a haloformic acid, in a suitable organic solvent. Also disclosed are processes for preparing paroxetine comprising hydrolyzing the novel carbamate intermediates in a suitable solvent. Paroxetine prepared by the above processes can be neutralized with hydrogen chloride and crystallized as paroxetine hydrochloride anhydrous, hemihydrate or as a solvate of isopropanol. The invention is further directed to the novel carbamate intermediates formed by the disclosed processes.

1 . A compound of formula (VII):  
     
       
         
         
             
             
         
       
       wherein R 1  is a haloalkyl other than 1-monohaloalkyl or perfluoroalkyl.  
     
   
   
       2 . The compound of  claim 1 , wherein R 1  is a 2-haloalkyl.  
   
   
       3 . The compound of  claim 2 , wherein R 1  is a 2-chloroalkyl.  
   
   
       4 . The compound of  claim 3 , wherein R 1  is 2-chloroethyl.  
   
   
       5 . The compound of  claim 3 , wherein R 1  is 2,2,2-trichloroethyl  
   
   
       6 . A process for preparing a compound of formula (VII) comprising reacting a compound of formula (V) with a compound of formula (VI) in a suitable organic solvent,  
     
       
         
         
             
             
         
       
       wherein Z is a halogen;  
       R 1  is a haloalkyl other than 1-monohaloalkyl or perfluoroalkyl, and  
       R 2  is a lower alkyl.  
     
   
   
       7 . The process of  claim 6 , wherein R 1  is a 2-haloalkyl.  
   
   
       8 . The process of  claim 7 , wherein R 1  is a 2-chloroalkyl.  
   
   
       9 . The process of  claim 8 , wherein R 1  is 2-chloroethyl.  
   
   
       10 . The process of  claim 8 , wherein R 1  is 2,2,2-trichloroethyl.