Processes leading to enantiomerically pure compounds are of utmost importance, in particular for the pharmaceutical industry. Starting from a racemic mixture, crystallization‐induced diastereomeric transformation allows in theory for 100 % transformation of the desired enantiomer. However, this method has the inherent limiting requirement for the organic compound to form a salt. Herein, this limitation is lifted by introducing cocrystallization in the context of thermodynamic deracemization, with the process applied to a model chiral fungicide. We report a new general single thermodynamic deracemization process based on cocrystallization for the deracemization of (R,S)‐4,4‐dimethyl‐1‐(4‐fluorophenyl)‐2‐(1H‐1,2,4‐triazol‐1‐yl)pentan‐3‐one. This study demonstrates the feasibility of this novel approach and paves the way to further development of such processes.

Processes leading to enantiomerically pure compounds are of utmost importance, in particular for the pharmaceutical industry. Starting from a racemic mixture, crystallization‐induced diastereomeric transformation allows in theory for 100 % transformation of the desired enantiomer. However, this method has the inherent limiting requirement for the organic compound to form a salt. Herein, this limitation is lifted by introducing cocrystallization in the context of thermodynamic deracemization, with the process applied to a model chiral fungicide. We report a new general single thermodynamic deracemization process based on cocrystallization for the deracemization of (R,S)‐4,4‐dimethyl‐1‐(4‐fluorophenyl)‐2‐(1H‐1,2,4‐triazol‐1‐yl)pentan‐3‐one. This study demonstrates the feasibility of this novel approach and paves the way to further development of such processes.

Processes leading to enantiopure compounds are of utmost importance, in particular for the pharmaceutical industry. Starting from a racemic mixture, Crystallization Induced Diastereomeric Transformation allows for a theoretical 100% transformation of the desired enantiomer. However, this method has the inherent limiting requirement for the organic compound to form a salt. In this contribution, this limitation is lifted by introducing cocrystallization in the context of thermodynamic deracemization, with the process applied to a model chiral fungicide. We here report a new general single thermodynamic deracemization process based on co-crystallization for the deracemization of (R,S)-4,4-dimethyl-1-(4-fluorophenyl)-2-(1H-1,2,4-triazol-1-yl)-Pentan-3-one. This work presents the feasibility of this novel approach and paves the way to further development of such processes.With the increasing number of enantiopure chiral drugs developed every year [1] and regulatory instances encouraging the development of enantiopure compounds [2] , processes allowing access to these, are of utmost importance. In spite of significant advances in asymmetric synthesis (in particular asymmetric catalysis), the most prominent way to enantiopure drugs nowadays still involves formation of a racemic compound [3] and separation of the unwanted enantiomer through a resolution process [4][5][6][7][8] , or its transformation into the desired enantiomer, in a so-called deracemization process. Crystallization-based resolution processes are less costly than eg. chromatographically based techniques and therefore industrially wide-spread. Typical crystallization based resolution processes are preferential crystallization [9][10][11] and diastereomeric resolution. [12][13][14] Going beyond separation, crystallization based deracemization processes aim at transforming the unwanted enantiomer (distomer) into the desired one (eutomer). Over the recent years, different deracemization tools were developed. The kinetic process of Viedma Ripening (VR) [15,16] and Dynamic Preferential Crystallization (DPC) [17] require a conglomerate forming racemate and are therefore inherently limited to 5-10% of all compounds. Crystallization Induced Diastereomeric Transformation--CDIT [18,19] , on the other hand, is a thermodynamical approach, based on the differences in solubility between two diastereomeric salts and does therefore not require the formation of such a conglomerate.Scheme 1 State of the art regarding deracemization and how Co-crystallization induced spontaneous deracemization (CoISD) redistributes the cards and opens new possibilities in the world of deracemization.

Processes leading to enantiopure compounds are of utmost importance, in particular for the pharmaceutical industry. Starting from a racemic mixture, Crystallization Induced Diastereomeric Transformation allows for a theoretical 100% transformation of the desired enantiomer. However, this method has the inherent limiting requirement for the organic compound to form a salt. In this contribution, this limitation is lifted by introducing cocrystallization in the context of thermodynamic deracemization, with the process applied to a model chiral fungicide. We here report a new general single thermodynamic deracemization process based on co-crystallization for the deracemization of (R,S)-4,4-dimethyl-1-(4-fluorophenyl)-2-(1H-1,2,4-triazol-1-yl)-Pentan-3-one. This work presents the feasibility of this novel approach and paves the way to further development of such processes.With the increasing number of enantiopure chiral drugs developed every year [1] and regulatory instances encouraging the development of enantiopure compounds [2] , processes allowing access to these, are of utmost importance. In spite of significant advances in asymmetric synthesis (in particular asymmetric catalysis), the most prominent way to enantiopure drugs nowadays still involves formation of a racemic compound [3] and separation of the unwanted enantiomer through a resolution process [4][5][6][7][8] , or its transformation into the desired enantiomer, in a so-called deracemization process. Crystallization-based resolution processes are less costly than eg. chromatographically based techniques and therefore industrially wide-spread. Typical crystallization based resolution processes are preferential crystallization [9][10][11] and diastereomeric resolution. [12][13][14] Going beyond separation, crystallization based deracemization processes aim at transforming the unwanted enantiomer (distomer) into the desired one (eutomer). Over the recent years, different deracemization tools were developed. The kinetic process of Viedma Ripening (VR) [15,16] and Dynamic Preferential Crystallization (DPC) [17] require a conglomerate forming racemate and are therefore inherently limited to 5-10% of all compounds. Crystallization Induced Diastereomeric Transformation--CDIT [18,19] , on the other hand, is a thermodynamical approach, based on the differences in solubility between two diastereomeric salts and does therefore not require the formation of such a conglomerate.Scheme 1 State of the art regarding deracemization and how Co-crystallization induced spontaneous deracemization (CoISD) redistributes the cards and opens new possibilities in the world of deracemization.