A concept for the chiral resolution of racemic compounds by a combination of chiral pre-enrichment by continuous multi-column chromatography and final purification using selective crystallization is presented. The system of serine enantiomers in water represents a typical racemic compound-forming system with very high eutectic compositions in the chiral system, which is generally considered as unfavorable for selective crystallization. It is shown exemplarily, how the solvent and temperature-dependent formation of hydrates can be exploited to allow efficient chiral resolution by a combined process for this and similar systems. (C) 2012 Elsevier B.V. All rights reserved.