Doubly tethered tertiary amide selectors: Modified version of Doyle et al.'s naproxen chiral stationary phase

The synthesis of an (S)-naproxen-derived chiral stationary phase (CSP) that differs from those of Doyle et al. [T.D. Doyle, C.A. Brunner and E. Smith, US Pat., 4919 803 (1990) and T.D. Doyle, in W.J. Lough (Editor), Chiral Liquid Chromatography, Chapman & Hall, New York, 1989, pp. 102-128] and of Oliveros et al. [L. Oliveros, C. Minguillón, B. Desmaziéres and P. Desbéne, J. Chromatogr., 589 (1992) 53 and 606 (1992) 9] is reported. Instead of linking naproxen to a primary amino group in the tether, linkage is to a secondary amino group. This avoids the presence of an amide hydrogen which often serves to increase retention, attenuate enantioselectivity and diminish the efficiency of the CSP. The presently described CSP 2 typically shows improved performance relative to those described by the Doyle et al. and Oliveros et al.