Preferential crystallization induced by chiral surfaces is an interesting alternative to isolate enantiopure antipodes. Herein, we take advantage of the outstanding enantiorecognition capabilities of inherently chiral oligomers to induce an...

Chirality plays an important role in the pharmaceutical industry since the two enantiomers of a drug molecule usually display significantly different bioactivities, and hence, most products are produced as pure enantiomers. However, many drug precursors are synthesized as racemates, and hence, enantioseparation has become a significant process in the industry. Cocrystallization is one of the attractive crystallization approaches to obtain the desired enantiomer from racemic compounds. In this work, we propose a chiral resolution route for an antiepileptic drug, S -etiracetam ( S -ETI), via enantiospecific cocrystallization with S -2-chloro- S -mandelic acid (CLMA) as a coformer. The experiments indicate that the system is highly enantiospecific; S -2CLMA cocrystallizes only with S -ETI but not with R -ETI or RS -ETI. Therefore, the chiral purification of S -ETI can be achieved efficiently with a 69.1% yield and close to 100% enantiopurity from the racemic solution. Additionally, structural simulations of the S -ETI: S -2CLMA cocrystal reveal that the cocrystal structure has higher thermodynamic stability than that of R -ETI: S -2CLMA by about 5.5 kcal/mol (per cocrystal formula unit), which helps to confirm the favorability of the enantiospecification in this system.