CC BY-ND-NC 4.0 · SynOpen 2019; 03(02): 55-58
DOI: 10.1055/s-0037-1611845
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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

Wade P. Winton
a  Division of Nuclear Medicine, Department of Radiology, The University of Michigan Medical School, 1150 W Medical Center Dr., Ann Arbor, Michigan, 48109, USA   Email: afb@umich.edu
,
Allen F. Brooks*
a  Division of Nuclear Medicine, Department of Radiology, The University of Michigan Medical School, 1150 W Medical Center Dr., Ann Arbor, Michigan, 48109, USA   Email: afb@umich.edu
,
Ka Kit Wong
a  Division of Nuclear Medicine, Department of Radiology, The University of Michigan Medical School, 1150 W Medical Center Dr., Ann Arbor, Michigan, 48109, USA   Email: afb@umich.edu
,
a  Division of Nuclear Medicine, Department of Radiology, The University of Michigan Medical School, 1150 W Medical Center Dr., Ann Arbor, Michigan, 48109, USA   Email: afb@umich.edu
,
Benjamin L. Viglianti
a  Division of Nuclear Medicine, Department of Radiology, The University of Michigan Medical School, 1150 W Medical Center Dr., Ann Arbor, Michigan, 48109, USA   Email: afb@umich.edu
b  Nuclear Medicine Service, Ann Arbor Veterans Administration, 2215 Fuller Rd, Ann Arbor, Michigan, 48105, USA
› Author Affiliations
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.
Further Information

Publication History

Received: 25 April 2019

Accepted after revision: 09 May 2019

Publication Date:
22 May 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

 
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