Synthesis and HPLC enantioseparation of the cyclopropane analogue of valine (c3Val).
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(4H)-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 x 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.
Jiménez
Ana I
AI
Departamento de Química Orgánica, ICMA, Universidad de Zaragoza-CSIC, Zaragoza, Spain.
López
Pilar
P
Cativiela
Carlos
C
D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003521:Cyclopropanes / Q000737:chemistry*; D013237:Stereoisomerism; D014633:Valine / Q000031:analogs & derivatives*
D003521:Cyclopropanes; C030797:cyclopropane; D014633:Valine