Process for producing 3-amino-2-hydroxypropionic acid derivatives

Abstract

The present invention provides a process for preparing 3-amino-2-hydroxypropionic acid derivatives (1) which does not use dangerous reagents, is economically advantageous, and is suitable for an industrial production, which process comprises: treating N-protected-3-amino-2-hydroxypropionic acid derivatives (2) having a steric configuration at 2-position carbon reverse to that of derivatives (1) with a leaving group-introducing agent to convert into N-protected-3-aminopropionic acid derivatives (3), then treating the derivatives with a basic substance to convert into substituted-3-amino-2-hydroxypropionic acid derivatives (4) having an inverted steric configuration at 2-position carbon, and then converting the derivatives into 3-amino-2-hydroxypropionic acid derivatives (1).

1 - 28 . (canceled)  
   
   
       29 . A process for crystallizing 3-amino-2-hydroxypropionic acid derivative, which comprises: 
 preparing a 3-amino-2-hdroxypropionic acid derivative represented by the general formula (1):                          wherein R 1 , R 2  and R 3 , independently from each other, represent a hydrogen atom, a substituted or unsubstituted alkyl group having 1 to 30 carbon atoms, a substituted or unsubstituted aryl group having 6 to 30 carbon atoms, or a substituted or unsubstituted aralkyl group having 7 to 30 carbon atoms, which comprises the steps of:    converting a N-protected-3-amino-2-hydroxyp-ropionic acid derivative having a steric configuration at 2-position carbon reverse to that of the above compound (1) and represented by the general formula (2):                          wherein R 1 , R 2  and R 3  are as defined above;    S 1  represents an urethane-type protecting group for an amino group represented by —COOR 4 , wherein R 4  represents a substituted or unsubstituted alkyl group having 1 to 30 carbon atoms, a substituted or unsubstituted aryl group having 6 to 30 carbon atoms, or a substituted or unsubstituted aralkyl group having 7 to 30 carbon atoms; and    S 2  represents a hydrogen atom or an ester residue;    by a reaction for introducing a leaving group, into a N-protected-3-aminopropionic acid derivative represented by the general formula (3):                          wherein R 1 , R 2  and R 3  and S 1  are as defined above;    L represents a leaving group selected from the group consisting of a sulfonyloxy group, a halosulfinyloxy group and a halogen atom; and    S 3  represents a hydrogen atom or an ester residue;    then converting the derivative (3), by a reaction for inverting the steric configuration at 2-position, into a substituted-3-amino-2-hydroxypropionic acid derivative having an inverted steric configuration at 2-position carbon and represented by the general formula (4):                          wherein R 1 , R 2  and R 3  are as defined above:    S 4  represents a hydrogen atom or an ester residue;    S 5  represents a hydrogen atom or a substituent derived from S 1 ;    S 6  represents S 1  when S 5  is a hydrogen atom, or a substituent derived from S 1 , taken together with S 5 , when S 5  is a substituent derived from S 1 ; and    S 1  is as defined above; 
 and then converting the derivative (4), by a reaction for removing substituents S 4 , S 5  and S 6 , into 3-amino-2-hydroxypropionic acid derivative (1)  
   converting an acid or a base coexisting in an acidic or basic aqueous solution of 3-amino-2-hydroxypropionic acid derivative (1) into a salt soluble in an organic solvent and/or water by neutralization using a base or an acid,    whereby precipitating 3-amino-2-hydroxypropionic acid derivative (1) from a medium consisting of water or a mixture of an organic solvent and water, and at the same time, dissolving the above salt formed in said medium.    
   
   
       30 . A process for crystallizing 3-amino-2-hydroxypropionic acid derivative (1) represented by the general formula (1):  
     
       
         
         
             
             
         
       
     
     wherein R 1 , R 2  and R 3 , independently from each other, represent a hydrogen atom, a substituted or unsubstituted alkyl group having 1 to 30 carbon atoms, a substituted or unsubstituted aryl group having 6 to 30 carbon atoms, or a substituted or unsubstituted aralkyl group having 7 to 30 carbon atoms, which comprises; 
 converting an acid or a base coexisting in an acidic or basic aqueous solution of 3-amino-2-hydroxypropionic acid derivative (1) into a salt soluble in an organic solvent and water by neutralization using a base or an acid,  
 whereby precipitating 3-amino-2-hydroxypropionic acid derivative (1) from a medium consisting of water or a mixture of an organic solvent and water, and at the same time, dissolving the above salt formed in said medium.  
 
   
   
       31 . The process according to  claim 30  wherein the salt soluble in an organic solvent and water is a lithium salt.  
   
   
       32 . The process according to  claim 30  wherein an acidic aqueous solution of 3-amino-2-hydroxypropionic acid derivative (1) is neutralized using a basic lithium compound.  
   
   
       33 . The process according to  claim 30  wherein a basic aqueous solution of 3-amino-2-hydroxypropionic acid derivative (1) consists of 3-amino-2-hydroxypropionic acid derivative (1) and a basic lithium compound.  
   
   
       34 . The process according to  claim 30  wherein the organic solvent is a water-soluble organic solvent.  
   
   
       35 - 36 . (canceled)  
   
   
       37 . The process according to  claim 31  wherein an acidic aqueous solution of 3-amino-2-hydroxypropionic acid derivative (1) is neutralized using a basic lithium compound.  
   
   
       38 . The process according to  claim 31  wherein a basic aqueous solution of 3-amino-2-hydroxypropionic acid derivative (1) consists of 3-amino-2-hydroxypropionic acid derivative (1) and a basic lithium compound.  
   
   
       39 . The process according to  claim 31  wherein the organic solvent is a water-soluble organic solvent.