Coupling of simulated moving bed chromatography and fractional crystallisation for efficient enantioseparation

An optimised coupling of liquid chromatography and fractional crystallisati on is suggested for efficient enantioseparation. As a first stage, a chroma tographic separation, preferably simulated moving bed (SMB) chromatography, is applied to achieve an enantiomeric enrichment sufficient for a subseque nt crystallisation. First results of the experimental and modelling work fo r the model system (+)-/(-)-mandelic acid in an aqueous solution are descri bed. Chromatographic investigations involve the estimation of adsorption is otherms on a suitable chiral stationary phase and the simulation and optimi sation of a corresponding SMB process. From the ternary phase diagram measu red for the (+)-/(-)-enantiomer/solvent system, the conditions required to crystallise a pure enantiomer from an asymmetric mixture can be derived. Th e productivity gains achievable from the combined process compared to the a pplication of chromatography alone are discussed. (C) 2001 Elsevier Science B.V. All rights reserved.