Process For Making N-(Diphenylmethyl)piperazines

Abstract

The compound of formula (8), in racemic or single enantiomeric form, is useful in making N-(diphenylmethyl)-piperazines such as cetirizine and levocetrizine. wherein Z is preferably phenyl.

1 . A compound of formula (7) 
       
         
           
           
               
               
           
         
       
       wherein X is a leaving group reactive with an amine; and
 Z is a C7-C20 aralkyl group or a C6-C20 aryl/alkylaryl group, each of which groups can be substituted by one to four alkoxy groups. 
 
     
     
         2 . The compound according to  claim 1 , wherein X is a halo group or a sulphonyl group. 
     
     
         3 . The compound according to  claim 1 , wherein Z is selected from phenyl, p-tolyl, p-methoxyphenyl, and benzyl. 
     
     
         4 . The compound according to  claim 1 , wherein said compound of formula (7) is N,N-bis(2-chloroethyl)phenyl carbamate of formula (7a) 
       
         
           
           
               
               
           
         
       
     
     
         5 . A compound of formula (8) 
       
         
           
           
               
               
           
         
         wherein Z is a C7-C20 aralkyl group or a C6-C20 aryl/alkylaryl group, each of which groups can be substituted by one to four alkoxy or amino groups. 
       
     
     
         6 . The compound according to  claim 5 , wherein said compound is substantially the (R) enantiomer. 
     
     
         7 . The compound according to  claim 6 , wherein said compound has an optical purity of at least 95%. 
     
     
         8 . The compound according to  claim 6 , wherein Z is phenyl. 
     
     
         9 . A crystalline oxalic acid addition salt of a compound of formula (4) 
       
         
           
           
               
               
           
         
       
     
     
         10 . The crystalline salt according to  claim 9 , wherein said compound of formula (4) is substantially the (R) enantiomer. 
     
     
         11 . The compound according to  claim 10 , wherein said compound of formula (4) has an optical purity of at least 95%.