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The use of tetrabutylammonium fluoride to promote N ‐ and O ‐ 11 C‐methylation reactions with iodo[ 11 C]methane in dimethyl sulfoxide
Author(s) -
Kikuchi Tatsuya,
Minegishi Katsuyuki,
Hashimoto Hiroki,
Zhang MingRong,
Kato Koichi
Publication year - 2013
Publication title -
journal of labelled compounds and radiopharmaceuticals
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.432
H-Index - 47
eISSN - 1099-1344
pISSN - 0362-4803
DOI - 10.1002/jlcr.3092
Subject(s) - chemistry , methylation , tetrabutylammonium fluoride , fluoride , radiochemistry , dimethyl sulfoxide , methane , sulfoxide , medicinal chemistry , inorganic chemistry , organic chemistry , catalysis , biochemistry , gene
The N ‐ or O ‐methylation reactions of compounds bearing amide, aniline, or phenol moieties using iodo[ 11 C]methane (1) with the aid of a base are frequently applied to the preparation of 11 C‐labeled radiopharmaceuticals. Although sodium hydride and alkaline metal hydroxides are commonly employed as bases in these reactions, their poor solubility properties in organic solvents and hydrolytic activities have sometimes limited their application and made the associated 11 C‐methylation reactions difficult. In contrast to these bases, tetrabutylammonium fluoride (TBAF) is moderately basic, highly soluble in organic solvents, and weakly nucleophilic. Although it was envisaged that TBAF could be used as the preferred base for 11 C‐methylation reactions using 1, studies concerning the use of TBAF to promote 11 C‐methylation reactions are scarce. Herein, we have evaluated the efficiency of the 11 C‐methylation reactions of 13 model compounds using TBAF and 1. In most cases, the N ‐ 11 C‐methylations were efficiently promoted by TBAF in dimethyl sulfoxide at ambient temperature, whereas the O ‐ 11 C‐methylations required heating in some cases. Comparison studies revealed that the efficiencies of the 11 C‐methylation reactions with TBAF were comparable or sometimes greater than those conducted with sodium hydride. Based on these results, TBAF should be considered as the preferred base for 11 C‐methylation reactions using 1.