Optical resolution of baclofen via diastereomeric salt pair formation between 3-(p-chlorophenyl)glutaramic acid and (S)-(-)-α-phenylethylamine

Abstract

The structures of the diastereomeric salts of (R)-(+)- and (S)-(-)-3-(p -chlorophenyl)glutaramic acid with (S)-(-)-phenylethylamine have been determined by X-ray crystallography. Solubility and melting behaviours of the salts were analysed and correlated with their structural properties in the solid state. The (R)-(+)-3-(p-chlorophenyl)glutaramic acid was converted to (R)-(-)-baclofen via a Hofmann degradation (57% yield, 99.8% ee, enantiomeric excess).

References

1. K. Rudnick and K. Bochow, Ger. Pat. DD 234 162, 1986; Chem. Abstr. 1987, 106, 4530c.
2. P. Hudgson and D. Weightman, Brit. Med. J., 1971, 4, 15.
3. H. R. Olpe, H. Demiéville, V. Baltzer, W. L. Benzce, W. P. Koella, P. Wolf and H. L. Haas, Eur. J. Pharmacol., 1978, 52, 133.
4. C. H. Chang, D. S. C. Yang, C. Y. Chung, W. Bi-Cheng, J. Pletcher, M. Sax and C. F. Terrence, Acta Crystallogr., Sect. B, 1982, 38, 2065.
5. (a) E. W. Wuis, E. W. J. Beneken Kolmer, L. E. C. van Beijsterveld, R. C. M. Burgers, T. B. Vree and E. v. d. Kleyn, J. Chromatogr., 1987, 451, 419; (b) C. Vaccher, P. Berthelot and M. Debaert, J. Chromatogr., 1993, 45, 95; (c) A. Sano, S. Takitani and H. Nakamura, Kuromatogurafi, 1994, 15(4), 234.
6. (a) C. Herdies and H. P. Hubmann, Tetrahedron Asymmetry, 1992, 3(9), 1213; (b) A. Shoenfelder, A. Mann and S. Le Coz, Synlett, 1993, 1, 63; (c) S. Yoshifuji and M. Kaname, Chem. Pharm. Bull., 1995, 43, 1302.
7. R. Chênevert and M. Desjardins, Can. J. Chem., 1994, 72, 2312.
8. Chirality in Industry. A. N. Collins, G. N. Sheldrake and J. Crosby, ed., Wiley, London, 1992, p. 20.
9. M. Sobocinska, G. Kupryszewski and M. M. Zobaczewa, Rocz. Chem., 1974, 48, 461.
10. N. A. Sivov, R. A. Gracheva, V. M. Potapov, L. G. Polevoi and I. P. Neumyvakin, Otkrytiya, Izobret., Prom. Obraztsy, Tovarnye Znaki, 1981, 17, 88[Pat. USSR827480/7 May ( 1981)].
11. F. Morlacchi, V. Losacco and V. Tortorella, Gazz. Chim. Ital., 1975, 105, 349.
12. See for example: (a) R. Yoshioka, O. Ohtsuki, T. Da-Ta, K. Okamura and M. Senuma, Bull. Chem. Soc. Jpn., 1994, 67, 3012; (b) F. J. J. Leusen, H. J. Bruins Slot, J. H. Noordijk, A. D. van der Haest, H. Wynberg and A. Bruggink, Recl. Trav. Chim. Pays-Bas, 1992, 111, 111; (c) M. Czugler, I. Csöregh, A. Kálmán, F. Faigl and M. Ács, J. Mol. Struct., 1989, 196, 157.
13. K. Yvon, W. Jeitschko and E. J. Parthé, J. Appl. Crystallogr., 1977, 10, 73.
14. A. C. T. North, D. C. Philips and F. S. Matthews, Acta Crystallogr., Sect. A, 1968, 24, 351.
15. G. M. Sheldrick, SHELX-86, in Crystallographic computing 3, eds. G. M. Sheldrick, C. Kruger and R. Goddard, Oxford University Press, Oxford, 1985, p. 175.
16. G. M. Sheldrick, SHELX-93: A program for Crystal Structure Determination, J. Appl. Crystallogr., in preparation, 1993.
17. H. D. Flack and D. Swarzenbach, Acta Crystallogr., Sect. A, 1988, 44, 499.
18. D. Kozma, G. Pokol and M. Ács, J. Chem. Soc., Perkin Trans. 2, 1992, 435.
19. E. Fogassy, A. Lopata, F. Faigl, F. Darvas and M. Ács, Tetrahedron Lett., 1980, 21, 647.
20. R. Taylor, O. Kennard and W. Versichel, Acta Crystallogr., Sect. B, 1984, 40, 280.
21. P. Murray-Rust and T. Glusker, J. Am. Chem. Soc., 1984, 106, 1018.
22. A. Vedani and J. D. Dunitz, J. Am. Chem. Soc., 1985, 107, 7653.
23. F. Toda, Supramolecular Chemistry, 1995, 6, 159.
24. M. Ács, Acta Chim. Hung.—Models in Chemistry, 1995, 132, 409.