Process strategies for batch preferential crystallization

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Chiral compounds, known as enantiomers, share identical physical and chemical properties but can have vastly different effects in biological systems. Nature has favored one enantiomer over the other in the evolution of living organisms, enabling them to differentiate between these molecules. This distinction can lead to severe consequences, particularly in pharmaceuticals, as highlighted by the thalidomide tragedy. This incident underscored the necessity of providing chiral active pharmaceutical ingredients as single enantiomers rather than as racemates. However, synthesizing one enantiomer selectively is challenging and often requires the final product to be in solid form, necessitating additional steps like crystallization or precipitation. An alternative approach involves separating racemates, with crystallization being an appealing method that integrates separation and solid formation. Preferential crystallization is a technique that allows for the direct crystallization of single enantiomers from racemic solutions. This work focuses on a systematic investigation of preferential crystallization, aiming to enhance robustness and yield while optimizing process conditions through the exploration of novel operating modes.