(114e) Resolution of a Chiral Racemate by Batch Chromatography, Batch Chromatography with Recycle, and Two-Column Semi-Continuous Simulated Moving Bed
Over the past decades there has been an increased interest on the separation of chiral molecules, especially those of particular importance in the biochemistry and pharmaceutical industries, which are subject to strict constrains on product purity imposed by pharmaceutical and food regulatory organizations, such as the American FDA .
One of the most common methods used in the resolution of chiral racemates is chromatography, where the conventional batch mode operation is, with some recent exceptions by means of multicolumn applications—notably simulated moving-bed processes, the predominant process in most preparative and process-scale separations. These recent multicolumn applications allow the possibility of reducing the mobile phase consumption and optimizing the usage of the stationary phase, therefore increasing the productivity and reducing production costs.
In the present work, a series of streamlined two-column processes for semi-continuous enantiomeric separation are assessed both numerically and experimentally and are compared against batch chromatography and batch chromatography with recycle. These processes exploit the benefits of simulated counter-current adsorption having a flexible node design, robust pump configuration, and cyclic flow-rate modulation. We have explored two cases of elution strategy: continuous elution, which has already been validated [2-4], and discontinuous elution; in the latter case the upstream column is frozen (the flow is halted) while fresh feed is injected into the downstream column. In our processes, fresh feed is supplied into the middle of the system where the composition of the circulating fluid is closest to that of the feedstock fluid, and the recovery of the purified products occurs alternately at the downstream end of the unit, while desorbent is supplied into the upstream end of the system.
The major advantage of this streamlined design is the simplicity of its physical realization; regardless of the number of columns it requires only two pumps—one to supply feed and another to supply desorbent into the system—and simple two-way valves to control the flow rates of liquid withdrawn from the system. The feasibility and effectiveness of the proposed processes have been verified experimentally for the nonlinear separation of troger’s base racemate in Chiralpak AD under overloaded conditions and subject to 99% purity constraints on both products.
 Food and Drug Administration, Chirality 4 (1992) 338-340.
 R.C.R. Rodrigues, T.J.S.B. Canhoto, J.M.M. Araújo and J.P.B. Mota, Two-column simulared moving-bed process for binary separation, J. Chromatogr. A 1180 (2008) 42-52.
 R.C.R. Rodrigues, R.J.S. Silva and J.P.B. Mota, Streamlined, two-column, simulated countercurrent chromatography for binary separation, J. Chromatogr. A 1217 (2010) 3382-3391.
 J.M.M. Araújo, R.C.R. Rodrigues, M.F.J. Eusébio and J.P.B. Mota, Chiral separation by two-column semi-continous, open-loop simulated moving-bed chromatography, J. Chromatogr. A 1217 (2010) 5407-5419.