Chiral purity limitation: discovery of a partial solid solution

Laureline Marc (1, 2) , Chrystal Lopes (1) , Jean-Marie Schneider (2) , Morgane Sanselme (1) , Gérard Coquerel (1)

1 SMS - Sciences et Méthodes Séparatives
2 SEQENS’Lab

Since S-Ibuprofen (S-Ibu) has been proved to have a higher therapeutic effect than R-Ibuprofen (R-Ibu) [1], the chiral separation of racemic Ibuprofen (rac-Ibu) -the current marketed drug- has become of great interest. In this work, chiral resolution of rac-Ibu was performed by using S-α-MethylBenzylAmine (S-αMBA) in order to form the diastereomeric salt S-Ibu-S-αMBA. The chiral purity obtained from various experiments seemed limited to a maximum of 87% of S-Ibu-S-αMBA. XRPD analysis suggested the existence of a partial solid solution, but the phase diagram published in literature [2] only exhibits a simple eutectic. Investigations performed through DSC measurements allowed the construction of Tammann graph and evidenced the existence of a partial solid solution enriched in S-Ibu-S-αMBA. This partial solid solution is the cause of the limitation in chiral purity. The updated phase diagram has been recently published [3]. [1] A. M. Evans, Clinical Rheumatology, 2001, vol. 20, p. 9-14. [2] E. J. Ebbers et al., Tetrahedron: Asymmetry, 1997, vol. 8, p. 4047-4057. [3] L. Marc et al., Crystals, 2021, vol. 11, p. 1188.

Domains: Chemical Sciences; Material chemistry; Chemical Sciences

Laureline Marc, Chrystal Lopes, Jean-Marie Schneider, Morgane Sanselme, Gérard Coquerel. Chiral purity limitation: discovery of a partial solid solution. Chirafun, Nov 2021, Rennes, France. ⟨hal-03455543⟩