Closed-loop recycling chromatography

Tailing of the peaks also creates significant problems (high consumption of mobile phases, strong dilutions, etc.) in recycling chromatography. Therefore, if only one enantiomer is desirable, it is preferable to elute it as the first peak. 

Chiral compound Chiral stationary phase Resolved amount, mg Reference 

Chlorthalidone Poly-N-acryloyl-(S)-phenylalanine ethyl ester diol silica 240 [148] 

Thalidomide Poly-N-methacryloyl-(R)-cyclo- hexyl-2-ethylamide 140 [148] 

In paying credit to the fact that the SMB is the most promising chromatographic technique for the production of enantiomerically pure chiral drugs, this technique is discussed below in a rather comprehensive way. Together with the principles, some strategies of method development are also addressed. 

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J. Dingenen and J. N. Kinkel, Preparative chromatographic resolution of racemates on chiral stationary phases on laboratory and production scales by closed-loop recycling chromatography , J. Chromatogr. 666 627 -650 (1994). 

Closed-loop recycling chromatography (reviewed by Dingenen and Kinkel 422)) may be necessary for separations of compt)unds with low enantioselectivity. 

The critical point in closed-loop recycling chromatography is the increase in axial dispersion due to the additional hold-up volume generated by the pump head and... 

Fig. 5.9 Closed-loop recycling chromatography with peak shaving.

Fig. 5.10 Development of concentrations during closed loop recycling chromatography operation with peak shaving.

Table 6. Selected examples of preparative enantioseparation of chiral drugs, drug candidates and drug intermediates using closed-loop recycling chromatography (CLRC)...

Figure 5.5 Closed-loop recycling chromatography with peak shaving. A corresponding chromatogram is shown in Figure 5.6.

Figure 7.17 Scale-up strategy for closed loop recycling chromatography.

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