Simulated Moving Bed in the Commercial Production of Sertraline

The search for a cost-effective synthetic method for the production of (4S)-tetralone 4, the intermediate on the pathway to sertraline, was shifted to technology that is still new to the pharmaceutical industry - continuous chromatographic separation 

The operating mode of SMB is illustrated in Fig. 7.3, which presents the 12-column system. The eluent and feed streams enter the chromatographic system cmitinuously. A counter-current solid stream is simulated by shifting the inlet ports periodically in the direction of the internal recycle flow. This leads to the desired separation of the feed components, two enantiomers in the case of separation of racemate, which can be withdrawn through the extract and raffinate ports which are redirected in the same manner as the inlets [46]. 

Conventional fixed bed chromatographic columns can be used in SMB, and the inlet and outlet ports to the unit are redirected periodically in the direction of the fluid flow to simulate, in a discontinuous manner, the continuous counter current movement of the chiral stationary phase (CSP), as presented in Fig. 7.3. Continuous 

Nowadays, SMB is the technology of choice for industrial separation of larger quantities of racemates, motivated by the following benefits  

In-process control of SMB separation has recently been improved by various automated on-line enantiomeric analysis systems. An example, comprising an analytical HPLC set-up with two UV detectors sharing the same light source, employed to monitor the internal composition profile, is presented in Fig. 7.4 [47]. 

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