Method for preparing enantiomerically enriched n-carboxyanhydride

Abstract

This disclosure relates to methods for preparing an enantiomerically enriched N-carboxyanhydride of an amino alpha acid of the formula (IIIa) or (IIIb): from a compound of the formula (IIa) or (IIb), respectively: wherein R1, R2, and R3 are as defined in the disclosure.

1 . A method for preparing an enantiomerically enriched α-amino acid N-carboxyanhydride of formula (IIIa) or (IIIb): 
       
         
           
           
               
               
           
         
         from the compound of formula (IIa) or (IIb) respectively: 
       
       
         
           
           
               
               
           
         
         wherein in the formulae:
 R1 and R2 denote, independently of one another, an alkyl, alkenyl, cycloalkyl, alkylcycloalkyl, alkylaryl or aryl group; and 
 R3 denotes an alkyl or alkylaryl group; 
 
         comprising the following steps:
 (i) bringing the compound of formula (IIa) or (IIb) respectively into contact with SOCl 2  in a solvent; 
 (ii) precipitating the N-carboxyanhydride formed in step (i) using a non-solvent; and 
 (iii) recovering the N-carboxyanhydride, 
 
         and not comprising any recrystallization step, nor a sublimation step of the N-carboxyanhydride. 
       
     
     
         2 . The method according to  claim 1 , wherein R3 denotes a methyl or ethyl group. 
     
     
         3 . The method according to  claim 1 , wherein R1 and R2 denote, independently of one another, a methyl or ethyl group. 
     
     
         4 . The method according to  claim 2 , wherein R1 and R2 denote, independently of one another, a methyl or ethyl group. 
     
     
         5 . The method according to  claim 1 , wherein R1, R2 and R3 denote a methyl group. 
     
     
         6 . The method according to  claim 1 , wherein the compound of formula (IIa) is prepared according to the following reaction: 
       
         
           
           
               
               
           
         
       
       in the presence of a base. 
     
     
         7 . The method according to  claim 1 , wherein the compound of formula or (IIb) is prepared according to the following reaction: 
       
         
           
           
               
               
           
         
       
       in the presence of a base. 
     
     
         8 . The method according to  claim 6 , in which the reaction constitutes a step preceding step (i). 
     
     
         9 . The method according to  claim 7 , in which the reaction constitutes a step preceding step (i). 
     
     
         10 . A method of preparing enantiomerically enriched N-carboxyanhydride of formula (A) or (B): 
       
         
           
           
               
               
           
         
         comprising the following steps:
 (i) bringing the compound of formula 
 
       
       
         
           
           
               
               
           
         
         
            or respectively 
         
       
       
         
           
           
               
               
           
         
         
           into contact with SOCl 2  in a solvent; 
           (ii) precipitating the N-carboxyanhydride formed in step (i) using a non-solvent; and 
           (iii) recovering the N-carboxyanhydride; 
         
         and not comprising any recrystallization step, nor a sublimation step of the N-carboxyanhydride. 
       
     
     
         11 . The method according to  claim 1 , wherein the reaction from step (i) is carried out at a temperature between −10 and 50° C. 
     
     
         12 . The method according to  claim 10 , wherein the reaction from step (i) is carried out at a temperature between −10 and 50° C. 
     
     
         13 . The method according to  claim 1 , wherein the reaction from step (i) is carried out with 1 to 3 equivalent(s) of SOCl 2  relative to the compound (IIa) or (IIb) respectively. 
     
     
         14 . The method according to  claim 10 , wherein the reaction from step (i) is carried out with 1 to 3 equivalent(s) of SOCl 2  relative to the compound (C) or (D) respectively. 
     
     
         15 . The method according to  claim 1 , wherein the reaction from step (i) is carried out with 1 to 3 equivalent(s) of SOCl 2  relative to the compound (IIa) or (IIb) respectively. 
     
     
         16 . The method according to  claim 10 , wherein the reaction from step (i) is carried out with 1 to 3 equivalent(s) of SOCl 2  relative to the compound (C) or (D) respectively. 
     
     
         17 . The method according to  claim 1 , wherein the non-solvent from step (ii) is a liquid alkane or an oil cut. 
     
     
         18 . The method according to  claim 10 , wherein the non-solvent from step (ii) is a liquid alkane or an oil cut. 
     
     
         19 . The method according to  claim 1 , wherein the solvent is a chlorinated solvent and the non-solvent is a liquid alkane or oil cut. 
     
     
         20 . The method according to  claim 1 , wherein the solvent is dichloromethane and the non-solvent is n-heptane. 
     
     
         21 . The method according to  claim 10 , wherein the solvent is dichloromethane and the non-solvent is n-heptane. 
     
     
         22 . The method according to  claim 1 , wherein the recovery of the N-carboxy-anhydride from step (iii) is a filtration/drying operation. 
     
     
         23 . The method according to  claim 10 , wherein the recovery of the N-carboxy-anhydride from step (iii) is a filtration/drying operation. 
     
     
         24 . A compound of formula: