(84e) Systematic Approach for Chiral Separation Via Diastereomeric Salt Formation

In order to prevent the possible complications, L- and D-enantiomers of pharmaceutical substances must be separated from each other. Direct separation is very difficult as enantiomers have identical physical and chemical properties. Unlike enantiomers diastereomeric salts possess different physical and chemical properties. The difference in properties endorsed diastereomeric salt resolution (classical resolution) to be one of the strong separation techniques for pure enantiomers. During the process enantiomers are treated with an optically active resolving agent to form diastereomeric salts that can be separated via crystallization. Often in industry, classical resolution is performed with limited data on phase behavior and metastable zone width data for diastereomeric salts. The separation process can be planned effectively and yield can be improved, if the above data is available.

In the present work the diastereomeric salt separation of DL-phenyl glycine is presented.  Pure salts of both D-and L-phenyl glycine with camphor-D-sulphonic acid were synthesized in the laboratory and characterized with the help of different analytical techniques like ¹H NMR, XRPD, DSC and Raman spectroscopy. Further, basic thermodynamic and kinetic data like solubility phase diagram and metastable zone width were measured in different solvents. On this basis different possibilities for the resolution of both salts were derived and executed in the laboratory.  The comparison of results and selection of best process out of all above possible separation processes will be discussed.