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Solid-phase Synthesis of [4.4] Spirocyclic Oximes
Published on: February 6, 2019
Novel synthesis of the ortho ester derivative of 4,5-epoxymorphinan
Akio Watanabe1, Toshitsugu Kai, Hiroshi Nagase
1School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
Abstract:
[reaction: see text]. A method was found for the novel synthesis of ortho ester derivatives that are potentially useful as selective epsilon opioid receptor ligands. An unexpected 17-(cyclopropylmethyl)-4,5alpha-epoxy-6alpha-hydroxy-3,7,7-trimethoxy-8-oxa-6,14-endoethanomorphinan was produced when 17-(cyclopropylmethyl)-4,5alpha-epoxy-3-methoxy-6alpha,14-dihydroxy-6beta-(1,3-dithia-2-yl)-morphinan was treated in methanol with trimethyl orthoformate and CuO/CuCl2. This ortho ester derivative was then converted to an ester with acid. The structure of the ortho ester was determined by 2D NMR (HMBC) and mass spectra.
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