Separation of enantiomers of a chiral epoxide by simulated moving bed chromatography

The paper deals with chiral separation by simulated moving bed (SMB) chroma tography. The separation of chiral epoxide enantiomers in microcrystalline cellulose triacetate using methanol as eluent is considered as illustrative example. The use of microcrystalline cellulose triacetate for the chromato graphic separation of enantiomers is first reviewed and a methodology for o btaining basic data (adsorption equilibrium isotherms, axial dispersion and mass transfer coefficient) is discussed. A model for the prediction of the cyclic steady-state performance of the SMB, based on the analogy with the true moving bed, is developed assuming multicomponent adsorption equilibria , axial dispersion flow and linear driving force approximation to describe the intraparticle mass transfer rate. The simulation package is used to pre dict the effect of operating variables on the process performance and to de fine the regions for enantiomer separation. A simple optimization procedure is proposed for choosing the best SMB operating conditions. This procedure is extensively tested for the separation of chiral epoxide enantiomers. Th e experimental operation of a SMB pilot unit was carried out for this syste m. Purities and recoveries higher than 90% were obtained for both extract a nd raffinate, using a 420 mi inventory of stationary phase. The SMB pilot a llows the continuous resolution of 52 g of racemic mixture per day and per liter of bed, with a solvent consumption of 0.4 l of mobile phase per gram of racemic mixture processed. The simulation package is also used to predic t the steady-state internal concentration profiles for the SMB operation wi th reasonable agreement with experimental results, (C) 1998 Elsevier Scienc e B.V. All rights reserved.