Synthesis and HPLC enantioseparation of the cyclopropane analogue of valine ( c 3 Val)

A new and efficient method is presented for the preparation of the N ‐Boc‐protected cyclopropane analogue of valine, 1‐( N‐tert ‐butoxycarbonyl)amino‐2,2‐dimethylcyclopropanecarboxylic acid, both in racemic and enantiomerically pure forms. Cyclopropanation of the exocyclic double bond of 2‐phenyl‐4‐isopropylidene‐5(4 H )‐oxazolone with diazomethane followed by elaboration of the heterocyclic moiety provided multigram quantities of the racemic target compound. Subsequent HPLC resolution of a racemic precursor on a noncommercial chiral stationary phase has given access to enantiomerically pure products. Almost 1.5 g of the first‐eluted enantiomer and 1.0 g of the second‐eluted enantiomer have been isolated in optically pure form using a 150 × 20 mm ID column containing mixed 10‐undecenoate/3,5‐dimethylphenylcarbamate of cellulose covalently bonded to allylsilica gel with a mixture of hexanes/ tert ‐butyl methyl ether/ethyl acetate as the mobile phase. Chirality 17:22–29, 2005. ©2004 Wiley‐Liss, Inc.