Open AccessSNAr Radiofluorination with In Situ Generated [18F]Tetramethylammonium Fluoride
Author(s) -
So Jeong Lee,
María T Morales-Colón,
Allen F. Brooks,
Jay Wright,
Katarina J. Makaravage,
Peter J. H. Scott,
Melanie S. Sanford
Publication year - 2021
Publication title -
journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.2
H-Index - 228
eISSN - 1520-6904
pISSN - 0022-3263
DOI - 10.1021/acs.joc.1c01491
Subject(s) - nucleophile , aryl , fluoride , tetramethylammonium , reagent , in situ , chemistry , combinatorial chemistry , organic chemistry , inorganic chemistry , catalysis , ion , alkyl
This report describes a method for the nucleophilic radiofluorination of (hetero)aryl chlorides, (hetero)aryl triflates, and nitroarenes using a combination of [ 18 F]KF·K 2.2.2 and Me 4 NHCO 3 for the in situ formation of a strongly nucleophilic fluorinating reagent (proposed to be [ 18 F]Me 4 NF). This method is applied to 24 substrates bearing diverse functional groups, and it generates [ 18 F](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 18 F-labeled HQ-415 for potential (pre)clinical use.