Resolution of Baclofenium Hydrogenomaleate By Using Preferential Crystallization. A First Case of Complete Solid Solution at High Temperature and a Large Miscibility Gap in the Solid State

The (R)- and (S)-baclofenium hydrogenomaleate system exhibits an extensive chiral discrimination in the solid state at room temperature. Nevertheless, above 145 °C, the critical temperature, a complete solid solution between the two enantiomers is stable. The 50–50 mixture does not form any racemic compound at any temperature, and at 20 °C, the two mirror phases show limited symmetrical solid solutions as the enantiomeric excess equals 98.5%. This is due to a large miscibility gap in the solid state. Close to room temperature, the racemic mixture can be resolved by preferential crystallization. The yield of the process can be enhanced in acidic aqueous solutions (e.g., in HCl aq 2 M), which increases the solubility.