Journal of Chromatography A, 1119 (2006) 156–162 Continuous chromatographic separation of a baclofen precursor (N-Boc-4-[p-chloro-phenyl]-2-pyrrolidone) in a simulated moving bed using a polysaccharide carbamate as chiral stationary phase Vinicius de Veredas a , Marcos Jos´ e Sousa Carpes b , Carlos Roque Duarte Correia b , Cesar Costapinto Santana a,∗ a Departamento de Processos Biotecnol´ ogicos, Faculdade de Engenharia Qu´ ımica, Universidade Estadual de Campinas (UNICAMP), C.P. 6066, 13083-970 Campinas, SP, Brazil b Departamento de Qu´ ımica Orgˆ anica, Instituto de Qu´ ımica, Universidade Estadual de Campinas (UNICAMP), C.P. 6066, 13083-970 Campinas, SP, Brazil Available online 19 January 2006 Abstract Liquid chromatography is known as one of the most flexible, efficient and cost-effective methods to resolve racemic mixture in order to attend the growing demand of the pharmaceutical industry for pure enantiomeric compounds. Cellulose tris(3,5-dimethylphenylcarbamate) is frequently used as a stationary phase for enantiomeric separations because of its attractive properties, including high enantioselectivity, high loading capacity and good mechanical stability. In this study, we investigated the usefulness of cellulose tris(3,5-dimethylphenylcarbamate) as the stationary phase and of ethanol and hexane mixtures as the mobile phases for the chromatographic separation of potential pharmaceutical intermediates. Using adsorption equilibrium data, we determined the optimal operational conditions for the separation of the N-Boc-4-[p-chloro-phenyl]-2-pyrrolidone enantiomers – a baclofen precursor – in a semi-preparative scale simulated moving bed unit. This unit was used to obtain high purity enantiomers on a scale of 1g/day. The outlet streams were analyzed by an on-line system that consisted of a UV–vis spectrophotometric unit, a polarimeter, and HPLC. Enantiomeric purities of up to 97% were obtained for the raffinate stream and up to 90% for the extract stream. © 2006 Elsevier B.V. All rights reserved. Keywords: SMB chromatography; Enantiomer separation; Preparative chromatography; (N-Boc-4-[p-chloro-phenyl]-2-pyrrolidone); Cellulose tris(3,5- dimethylphenylcarbamate) 1. Introduction The improvement of solute selectivity is a general theme in the field of separation processes. The power of modern synthetic chemistry, in conjunction with technologies in separation sci- ences, can be used to develop new agents and equipment with enhanced capacity for selective separation. Such associations can help meeting the growing demand of the pharmaceutical industry for efficient and cost-effective methods for purifying optical isomers [1]. Continuous preparative chromatography has been employed as an important process for the chemical manu- facture of several chiral compounds [2]. ∗ Corresponding author. Tel.: +55 19 37883917; fax: +55 19 37883890. E-mail address: santana@feq.unicamp.br (C.C. Santana). Simulated moving bed (SMB) is a large-scale version of tra- ditional high-performance liquid chromatography (HPLC), but unlike normal HPLC, SMB operates continuously, without loss of the enantiomeric purity in outlet streams. This process con- sists of simulating the countercurrent movement of the adsorbent bed by switching the positions of inlet and outlet streams to produce two outlet streams, one of which is rich in the more adsorbed component (extract stream), while the other is rich in the less adsorbed component (raffinate stream). This procedure is appropriate for binary separations such as required for race- mates. The SMB system has been used to separate components from racemic mixtures [3], since it can provide two enantiomers of a chiral molecule with sufficiently high purity and quanti- ties for clinical tests or even production stages. The variety of chiral selectors used as stationary phase and the vast number of racemic mixtures produced by the pharmaceutical industry make this technique a powerful tool and provide a stimulating 0021-9673/$ – see front matter © 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.chroma.2006.01.003