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Synfacts 2011(12): 1279-1279  
DOI: 10.1055/s-0031-1289321
Synthesis of Natural Products and Potential Drugs
© Georg Thieme Verlag Stuttgart ˙ New York

Synthesis of a TRPV1 Antagonist

Contributor(s): Philip Kocienski
K. J. Butcher, S. M. Denton, S. E. Field, A. T. Gillmore, G. W. Harbottle, R. M. Howard, D. A. Laity*, C. J. Ngono, B. A. Pibworth*
Pfizer Global Research and Development, Sandwich, UK
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Publication History

Publication Date:
18 November 2011 (online)

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Significance

The target molecule is a transient vanilloid receptor (TRPV1) antagonist that was of interest for the treatment of chronic pain. The key step in the synthesis, the RuPyBox-catalyzed cyclopropanation of C, gave a good yield of the cyclopropane E, but the enantiomeric and trans/cis ratios were poor (ca 4:1). A rather elaborate purification protocol was required to deliver the desired carboxylic acid as its (S)-1,2,3,4-tetra­hydro-1-naphthylamine salt I.