Novel phenylboronic acid compounds and intermediates and processes for the preparation thereof

Abstract

Vitamin D derivatives, notably non-steroidal vitamin D derivatives, are prepared from novel disubstituted phenylboronic acid compounds having the formula (I): and also from the novel intermediates having the formulae (1), (2), (3) and (10):

1 . A non-steroidal vitamin D analogue prepared from a disubstituted phenylboronic acid compound of the following structural formula (I): 
     
       
         
         
             
             
         
       
     
     in which:
 R1 is a hydrogen atom or an alkyl radical having from 1 to 4 carbon atoms, 
 R2 and R3, which may be identical or different, are each an alkyl radical having from 1 to 4 carbon atoms, and 
 R4 is the —B(OH) 2  radical or the radical of formula: 
 
     
       
         
         
             
             
         
       
     
   
   
       2 . The non-steroidal vitamin D analogue as defined by  claim 1 , having the structural formula (IV): 
     
       
         
         
             
             
         
       
     
     in which:
 R1 is a hydrogen atom or an alkyl radical having from 1 to 4 carbon atoms, 
 R2 and R3, which may be identical or different, are each an alkyl radical having from 1 to 4 carbon atoms, and 
 R′ 1  is an alkyl radical having from 1 to 4 carbon atoms. 
 
   
   
       3 . A process for the preparation of a non-steroidal vitamin D analogue as defined by  claim 2 , comprising:
 a) Suzuki coupling a compound having the formula (I):   
     
       
         
         
             
             
         
       
     
     in which:
 R1 is a hydrogen atom or an alkyl radical having from 1 to 4 carbon atoms, 
 R2 and R3, which may be identical or different, are each an alkyl radical having from 1 to 4 carbon atoms, and 
 R4 is the —B(OH) 2  radical or the radical of formula: 
 
     
       
         
         
             
             
         
       
     
     and an aryl bromide having the formula (II): 
     
       
         
         
             
             
         
       
       in which: 
       R′ 1  is an alkyl radical having from 1 to 4 carbon atoms, to obtain a compound of formula (10): 
     
     
       
         
         
             
             
         
       
       b) fusing the Suzuki reaction compound (1) with the benzyl bromide (11) in the presence of a base: 
     
     
       
         
         
             
             
         
       
       c) liberating the alcohol functions of the compound (11) to obtain the compound (IV).