Dutch resolution of racemic 4-hydroxy- and 4-fluorophenylglycine with mixtures of phenylglycine and (+)-10-camphorsulfonic acid

4-Hydroxyphenylglycine and 4-fluorophenylglycine can be resolved with (+)-1 0-camphorsulfonic acid only if DL- or D-(-)-phenylglycine is added. When us ing DL-phenylglycine this is co-resolved in this process. In this resolutio n process mixed crystals are formed of the (+)- 10-camphorsulfonic acid sal ts of the D-(-)enantiomers of phenylglycine and the pam substituted phenylg lycines. In the crystal lattice of the mixed salts approximately 25-30% of the D-(-)-phenylglycine molecules can be randomly replaced by D-(-)para sub stituted phenylglycines, resulting in the desired resolution. The overall n on-stoichiometric composition of the mixed crystals reflects to some extent the composition in solution. This behaviour is typical for solid solutions . The solid solution behaviour in this so called 'Dutch resolution' is prov en by differential scanning calorimetry (DSC), X-ray crystal structure dete rmination and powder diffraction. (C) 2000 Elsevier Science Ltd. All rights reserved.