Synthesis of [18F]-γ-Fluoro-α,β-unsaturated Esters and Ketones via Vinylogous 18F-Fluorination of α-Diazoacetates with [18F]AgF

Stephen Thompson; So Jeong Lee; Isaac M. Jackson; Naoko Ichiishi; Allen F. Brooks; Melanie S. Sanford; Peter J. H. Scott

doi:10.1055/s-0039-1690012

Synthesis, Table of Contents

Synthesis 2019; 51(23): 4401-4407
DOI: 10.1055/s-0039-1690012

special topic

Synthesis of [¹⁸F]-γ-Fluoro-α,β-unsaturated Esters and Ketones via Vinylogous ¹⁸F-Fluorination of α-Diazoacetates with [¹⁸F]AgF

Stephen Thompson

^aDepartment of Radiology, University of Michigan Medical School, Ann Arbor, MI 48109, USA Email: pjhscott@umich.edu

,

So Jeong Lee

^aDepartment of Radiology, University of Michigan Medical School, Ann Arbor, MI 48109, USA Email: pjhscott@umich.edu

,

Isaac M. Jackson

^aDepartment of Radiology, University of Michigan Medical School, Ann Arbor, MI 48109, USA Email: pjhscott@umich.edu

,

Naoko Ichiishi

^bDepartment of Chemistry, University of Michigan, Ann Arbor, MI 48109, USA Email: mssanfor@umich.edu

,

Allen F. Brooks

^aDepartment of Radiology, University of Michigan Medical School, Ann Arbor, MI 48109, USA Email: pjhscott@umich.edu

,

Melanie S. Sanford ∗

^bDepartment of Chemistry, University of Michigan, Ann Arbor, MI 48109, USA Email: mssanfor@umich.edu

,

Peter J. H. Scott ∗

^aDepartment of Radiology, University of Michigan Medical School, Ann Arbor, MI 48109, USA Email: pjhscott@umich.edu

› Author Affiliations

Abstract

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Published as part of the Special Topic Halogenation methods (with a view towards radioimaging applications)

Abstract

This communication reports a method for the vinylogous radiofluorination of α-diazoacetates to generate [¹⁸F]-γ-fluoro-α,β-unsaturated esters and ketones in moderate to good radiochemical yields. The method uses no-carrier-added [¹⁸F]AgF and is compatible with aromatic and non-aromatic substrates and a number of different functional groups. The labeling method is showcased in the synthesis of a fluorinated cholest-5-en-3-one derivative as well as a difluorinated product pertinent to drug discovery.

Key words

fluorine-18 - late-stage fluorination - PET radiochemistry - diazo chemistry - positron emission tomography

Full Text

References

References
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13 Radiochemical yields (RCY) are nonisolated and were calculated by % integrated area of the ¹⁸F-labelled product versus [¹⁸F]fluoride in a radio-TLC trace. Product identities were confirmed by radio-HPLC.
14 In addition to low RCYs, we were not able to synthesize reference standards to confirm the identity of [¹⁸F]7F and [¹⁸F]8F because of stability issues, which is consistent with Davies’ results. For example, they reported an NMR yield for the OMe product, but did not isolate it, suggesting that the compound is unstable.⁷
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16 Lights in the fume hood where the reactions occurred were turned off as a general precaution. However, ambient laboratory lighting was left on and we do not believe the chemistry is light sensitive.

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