Enantiomeric enrichment of enantiomeric mixture of alpha-amino acids used as synthetic intermediates for pharmaceuticals involves cold precipitation of racemate from solvent and separating pure enantiomer from remaining solution

摘要

Enantiomeric enrichment of an enantiomeric mixture of alpha -amino acids (I) to produce an enantiomeric excess of at least 65% involves cold precipitation of the racemate from a solvent and separation of the pure enantiomer from the remaining solution. Enantiomeric enrichment of an enantiomeric mixture of alpha -amino acids of formula R1-CH2-CH(NH-R2)-COOH (I) comprises: (1) dissolution at a temperature between 25[deg]C and the solvent reflux temperature of the enantiomer mixture in a solvent in which the racemate can precipitate in the cold, which comprises a cyclic ether (optionally substituted), a 1-3C chlorinated hydrocarbon or a 3-6C aliphatic ketone; (2) precipitation of the racemate by cooling and separation of the precipitate; (3) optionally decoloration of the remaining solution, and (4) separation of the pure enantiomer from the remaining solution. R15- or 6-membered heterocyclyl containing at least 1 N, S or O heteroatom (optionally substituted by halo or 1-6C alkyl or 6-14C aryl (optionally substituted by halo or 1-6C alkyl)), and R2a protective group.