SNAr Radiofluorination with In Situ Generated [18F]Tetramethylammonium Fluoride

So Jeong Lee; María T Morales-Colón; Allen F Brooks; Jay S Wright; Katarina J Makaravage; Peter J H Scott; Melanie S Sanford

doi:10.1021/acs.joc.1c01491

S_NAr Radiofluorination with In Situ Generated [¹⁸F]Tetramethylammonium Fluoride

J Org Chem. 2021 Oct 15;86(20):14121-14130. doi: 10.1021/acs.joc.1c01491. Epub 2021 Sep 10.

Authors

So Jeong Lee^{1

2}, María T Morales-Colón³, Allen F Brooks¹, Jay S Wright¹, Katarina J Makaravage³, Peter J H Scott¹, Melanie S Sanford³

Affiliations

¹ Department of Radiology, University of Michigan, Ann Arbor, Michigan 48109, United States.
² Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02114,United States.
³ Department of Chemistry, University of Michigan, Ann Arbor, Michigan 48109, United States.

Abstract

This report describes a method for the nucleophilic radiofluorination of (hetero)aryl chlorides, (hetero)aryl triflates, and nitroarenes using a combination of [¹⁸F]KF·K_2.2.2 and Me₄NHCO₃ for the in situ formation of a strongly nucleophilic fluorinating reagent (proposed to be [¹⁸F]Me₄NF). This method is applied to 24 substrates bearing diverse functional groups, and it generates [¹⁸F](hetero)aryl fluoride products in good to excellent radiochemical yields in the presence of ambient air/moisture. The reaction is applied to the preparation of ¹⁸F-labeled HQ-415 for potential (pre)clinical use.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Fluorides*
Fluorine Radioisotopes*
Quaternary Ammonium Compounds
Radiopharmaceuticals

Substances

Fluorine Radioisotopes
Quaternary Ammonium Compounds
Radiopharmaceuticals
tetramethylammonium
Fluorides

Grants and funding

R01 EB021155/EB/NIBIB NIH HHS/United States