Chemical Process For Preparation Of Intermediates

Abstract

The present invention relates to compounds useful as pharmaceutical intermediates, to processes for preparing the intermediates, to intermediates used in the processes, and to the use of the intermediates in the preparation of pharmaceuticals. In particular, the present invention concerns enantiomerically pure trans-cyclopropane carboxylic acid derivatives, processes for preparing the carboxylic acid derivatives and their use in preparing pharmaceuticals.

1 . A process for preparing a compound of formula IV 
       
         
           
           
               
               
           
         
       
       wherein R is an alkyl group, comprising:
 treating a compound of formula III 
 
       
         
           
           
               
               
           
         
         with a compound of formula 3 
       
       
         
           
           
               
               
           
         
         wherein R 1  and R 2  are, independently, alkyl. 
       
     
     
         2 . A process according to  claim 1  wherein the compound of formula 3 is triethyl phosphonoacetate. 
     
     
         3 . A process according to  claim 1  wherein R, R 1 , and R 2  are, independently, selected from methyl, ethyl, n-propyl, iso-propyl, n-butyl, and tert-butyl. 
     
     
         4 . A process according to  claim 1  further comprising converting the compound of formula IV to a compound of formula VII 
       
         
           
           
               
               
           
         
       
     
     
         5 . A process according to  claim 4  wherein the compound of formula IV is treated with ammonia in the presence of a suitable base. 
     
     
         6 . A process according to  claim 1  further comprising preparing the compound of formula III by treating a compound of formula II 
       
         
           
           
               
               
           
         
       
       with a base. 
     
     
         7 . A process for preparing a compound of formula IV 
       
         
           
           
               
               
           
         
       
       wherein R is an alkyl group, comprising:
 a) reducing a compound of formula I 
 
       
         
           
           
               
               
           
         
         to give a compound of formula II 
       
       
         
           
           
               
               
           
         
         b) treating the compound of formula II with a base to give a compound of formula III 
       
       
         
           
           
               
               
           
         
         c) treating the compound of formula III with a compound of formula 3 
       
       
         
           
           
               
               
           
         
         wherein R 1  and R 2  are, independently, selected from alkyl. 
       
     
     
         8 . A process according to  claim 7  wherein the compound of formula III is triethyl phosphonoacetate. 
     
     
         9 . A process according to  claim 7  wherein R, R 1  and R 2  are, independently, selected from methyl, ethyl, n-propyl, iso-propyl, n-butyl, and tert-butyl. 
     
     
         10 . A process according to  claim 7  further comprising converting the compound of formula IV to a compound of formula VII 
       
         
           
           
               
               
           
         
       
     
     
         11 . A process according to  claim 10  wherein the compound of formula IV is treated with ammonia in the presence of a suitable base. 
     
     
         12 . A process for preparing a compound of formula IV 
       
         
           
           
               
               
           
         
         wherein R is an alkyl group, comprising: 
         a) treating the compound of formula II 
       
       
         
           
           
               
               
           
         
       
       with a base; and
 b) treating the product of a) with a compound of formula 3 
 
       
         
           
           
               
               
           
         
         wherein R 1  and R 2  are, independently, selected from alkyl. 
       
     
     
         13 . A process according to  claim 12  wherein the base is sodium hydroxide. 
     
     
         14 . A process according to  claim 12  wherein R, R 1  and R 2  are, independently, selected from methyl, ethyl, n-propyl, iso-propyl, n-butyl, and tert-butyl. 
     
     
         15 . A process according to  claim 12  wherein the compound of formula 3 is triethyl phosphonoacetate. 
     
     
         16 . A process according to  claim 12  further comprising converting the compound of formula IV to a compound of formula VII 
       
         
           
           
               
               
           
         
       
     
     
         17 . A process according to  claim 16  wherein the compound of formula IV is treated with ammonia in the presence of a suitable base. 
     
     
         18 . A process for preparing a compound of formula VII 
       
         
           
           
               
               
           
         
       
       comprising treating the compound of formula IV 
       
         
           
           
               
               
           
         
       
       with ammonia in the presence of a suitable base. 
     
     
         19 . A process according to  claim 18  wherein the base is sodium methoxide. 
     
     
         20 . A process according to  claim 18  wherein the base is potassium methoxide. 
     
     
         21 . A compound of formula II 
       
         
           
           
               
               
           
         
       
       or formula III 
       
         
           
           
               
               
           
         
       
       or formula VII