Synthesis of fluorinated isoxazoles using SelectfluorTM: preparation and characterization of 4-fluoroisoxazole, 4,4,5-trifluoroisoxazoline and 4,4-difluoro-5-hydroxyisoxazoline systems from one-pot and multi-step processes

Sato, K.; Sandford, G.; Shimizu, K.; Akiyama, S.; Lancashire, M.J.; Yufit, D.S.; Tarui, A.; Omote, M.; Kumadaki, I.; Harusawa, S.; Ando, A.

Abstract

3,5-Disubstituted 4-fluoroisoxazole, 4,4,5-trifluoroisoxazoline and 4,4-difluoro-5-hydroxyisoxazoline products were obtained from reaction of the corresponding isoxazoles with SelectfluorTM depending upon the reaction conditions. Although the fluorinations proceeded using conventional heating, microwave (μW) irradiation considerably shortened reaction times and enabled a high yielding one-pot cascade fluorination-cyclization from simple diketone substrates. In addition, a related 4-fluoroisoxazole-3-carboxyamide derivative was synthesized.

Citation

Sato, K., Sandford, G., Shimizu, K., Akiyama, S., Lancashire, M., Yufit, D., …Ando, A. (2016). Synthesis of fluorinated isoxazoles using SelectfluorTM: preparation and characterization of 4-fluoroisoxazole, 4,4,5-trifluoroisoxazoline and 4,4-difluoro-5-hydroxyisoxazoline systems from one-pot and multi-step processes. Tetrahedron, 72(13), 1690-1698. https://doi.org/10.1016/j.tet.2016.02.026

• Journal Article Type: Article
• Acceptance Date: Feb 8, 2016
• Online Publication Date: Feb 10, 2016
• Publication Date: Mar 31, 2016
• Deposit Date: Feb 16, 2016
• Publicly Available Date: Feb 10, 2017
• Journal: Tetrahedron
• Print ISSN: 0040-4020
• Publisher: Elsevier
• Peer Reviewed: Peer Reviewed
• Volume: 72
• Issue: 13
• Pages: 1690-1698
• DOI: https://doi.org/10.1016/j.tet.2016.02.026
• Keywords: Fluoroheteroaromatic, Selective fluorination, 4-fluoroisoxazole, 4,4,5-trifluoroisoxazoline TRPV1 antagonist.
• Public URL: https://durham-repository.worktribe.com/output/1419399