title: 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.
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.
authors.affiliation: Departamento de Processos Biotecnológicos, Faculdade de Engenharia Química, Universidade Estadual de Campinas (UNICAMP), SP, Brazil.
authors.forename: Vinicius
authors.initials: V
authors.lastname: de Veredas
authors.forename: Marcos José Sousa
authors.initials: MJ
authors.lastname: Carpes
authors.forename: Carlos Roque Duarte
authors.initials: CR
authors.lastname: Correia
authors.forename: Cesar Costapinto
authors.initials: CC
authors.lastname: Santana
mesh_terms: D001418:Baclofen / Q000138:chemical synthesis*; D002482:Cellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid / Q000295:instrumentation / Q000379:methods*; D000431:Ethanol; D006586:Hexanes; D048448:Phenylcarbamates / Q000737:chemistry*; D011760:Pyrrolidinones / Q000302:isolation & purification*; D013237:Stereoisomerism
chemical_list: D006586:Hexanes; C513223:N-tert-butyloxycarbonyl-4-(4-chlorophenyl)-2-pyrrolidone; D048448:Phenylcarbamates; D011760:Pyrrolidinones; C065943:cellulose tris-3,5-dimethylphenyl-carbamate; D000431:Ethanol; D002482:Cellulose; D001418:Baclofen