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

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

So Jeong Lee  1   2 , María T Morales-Colón  3 , Allen F Brooks  1 , Jay S Wright  1 , Katarina J Makaravage  3 , Peter J H Scott  1 , Melanie S Sanford  3
Affiliations

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

So Jeong Lee et al. J Org Chem. .

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·K2.2.2 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.

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Figures

Figure 1.
Figure 1.. Substrate scope, a,b
aRCY was determined by radio-TLC and identity of final product was confirmed by HPLC. N.a. = not available. Reaction temperature was optimized to 110 °C for 618F, 1218F, 1318F, and 2118F. All other reactions were conducted at 100 °C; b For data using Me4NBF4 as an additive, see Supporting Information.
Scheme 1.
Scheme 1.
SNAr fluorination and radiofluorination with tetraalkylammonium fluoride salts
Scheme 2.
Scheme 2.
Synthesis of [18F]HQ415
Scheme 3.
Scheme 3.
Automation of SNAr radiofluorination with in situ Me4N18F
See this image and copyright information in PMC

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