(221a) On Processes Delivering a Pure Enantiomer from a Racemic Feed

There are several processes delivering the target enantiomer of a chiral compound from a racemic feed; they have different prerequisites: (i) the availability of a Chiral Stationary Phase for chiral chromatography based processes; (ii) the conglomerate-type phase behavior in the case of a class of interesting crystallization based techniques.

Simulated Moving Bed chromatography can achieve 100% recovery only by recycling the undesired enantiomer through racemization, and we provide a comparative assessment of the two cases, i.e. SMB with and without racemization.

Preferential crystallization can be operated continuosly in an MSMPR (Mixed Suspension Mixed Product Removal) crystallizer, and we provide design criteria for this.

For chiral compounds prone to nucleation of the undesired enantiomer batchwise deracemization via temperature cycles is a simple and effective alternative to continuous crystallization.

Racemization is key to achieve 100% recovery in all these cases, and the rate of racemization is crucial in determining the process performance.

Comparative assessment across technologies is very challenging and case-specific, but the approach that we present here is a valuable methodology for this purpose.