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

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 R1, R2 and R3, 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 R1, R2 and R3 are as defined above;
• S1 represents an urethane-type protecting group for an amino group represented by —COOR4, wherein R4 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
• S2 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 R1, R2 and R3 and S1 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
• S3 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 R1, R2 and R3 are as defined above:
• S4 represents a hydrogen atom or an ester residue;
• S5 represents a hydrogen atom or a substituent derived from S1;
• S6 represents S1 when S5 is a hydrogen atom, or a substituent derived from S1, taken together with S5, when S5 is a substituent derived from S1;
• and
• S1 is as defined above;
• and then converting the derivative (4), by a reaction for removing substituents S4, S5 and S6, 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.