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DOI: 10.1055/s-0037-1611845
Synthesis of 6-(Fluoromethyl)-19-norcholest-5(10)-en-3-ol, a Fluorinated Analogue of NP-59, using the Mild Fluorinating Reagent, TBAF(Pinacol)2
Authors
This work was supported by funding from the Center for the Discovery of New Medicine at the University of Michigan, Mi-Kickstart Award from The Michigan Translational Research and Commercialization (Viglianti and Brooks), and a University of Michigan Energy Institute Michigan Memorial Phoenix Project Seed Grant.
Publikationsverlauf
Received: 25. April 2019
Accepted after revision: 09. Mai 2019
Publikationsdatum:
22. Mai 2019 (online)
Abstract
For 45 years, efforts to prepare a fluorinated analogue of the scintiscanning/SPECT agent 6-(iodomethyl)-19-norcholest-5(10)-en-3-ol (NP-59) for development of a PET imaging agent have failed due to undesired elimination reactions and unexpected rearrangements observed while utilizing a wide variety of fluorinating conditions (e.g., cesium fluoride, silver fluoride, (2-chloro-1,1,2-trifluoroethyl)diethylamine (FAR), diethylaminosulfur trifluoride (DAST), and hexafluoropropene diethylamine FPA). Herein, we report the full synthesis of NP-59, followed by the four-step synthesis of 6-(fluoromethyl)-19-norcholest-5(10)-en-3-ol (FNP-59) using a recently developed mild fluorinating reagent, less prone to producing elimination reactions in the preparation of primary fluorides, TBAF(pinacol)2, with an overall yield of 16% (four steps). Also included is an evaluation of the TBAF(pinacol)2 reagent on eight test substrates to investigate its scope.
Supporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/s-0037-1611845.
- Supporting Information (PDF)
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References and Notes
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For recent reviews of fluorinated steroids, and use of their radiofluorinated derivatives in PET, see: