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@INPROCEEDINGS{Humpert:1026496,
author = {Humpert, Swen and Menges, Tobias and Keuthen, Yannick and
Zlatopolskiy, Boris and Neumaier, Bernd},
title = {{E}valuation of tetramethylammonium salts in
minimalist-like {SNA}r radiofluorinations},
reportid = {FZJ-2024-03440},
year = {2023},
abstract = {Objective: Tetraalkylammonium salts like Et 4NX or Bu4NX
repre-sent valuable alternatives to conventional K2 CO3
/K2.2.2., enablingpreprocessing of [ 18 F]fluoride without
azeotropic drying. Additionally,the selection of appropriate
counter ions like bicarbonate or triflateallow the
adjustment of the basic strength in the reaction medium,
e,g.,for radiolabeling of sensitive substrates or
Cu-mediated 18 F-fluorin-ation. Recently, NMe4 HCO 3 was
reported to improve the yield in SNArradiofluorination
reactions if added to azeotropically dried [ 18F]KF·K2.2.2.
The enhanced reactivity was attributed to in situ
formationof strongly nucleophilic [ 18 F]Me4 NF [1]. Herein,
we describe theazeotropic drying-free preparation of [ 18
F]Me4NF and evaluation of itsreactivity in SNAr 18
F-fluorinations compared to widely applied [18 F]Et
4NF.Methods: Aqueous [ 18 F]fluoride was loaded onto a QMA
cartridgeand the resin was washed with anhydrous MeOH. [18
F]F– was elutedwith a solution of the respective salt (18
µmol) in MeOH. Evaporationof MeOH directly afforded
anhydrous [ 18 F]R4 NF/X (R = Me, Et; X = OTf,HCO3 ) salts.
The latter were comparatively evaluated using a series
of(hetero)aromatic substrates containing various leaving
groups (-F, -Cl,-Br, -I, Me3 N-+, -NO2 , -OTf, DABCO-onium,
sulfonium and iodonium).Suboptimal reaction conditions (7
µmol of precursor, DMF, 100 °C,10 min) were intentionally
used to obtain significant differences inradiochemical
conversions (RCCs) even for highly reactive
precursors.Results: Minimalist preprocessing of [
18F]fluoride furnished therespective anhydrous [ 18F]NR4 F/X
in radiochemical yields of $>95\%within$ only 5 min. With
two exceptions concerning isotopic exchangeon heteroarenes
(entries 5 and 6), the RCCs for labeling of the
modelsubstrates were consistently higher for [ 18F]Me4NF/X
in comparison tothe corresponding [ 18 F]Et4 NF/X salt. On
average the absolute differenceamounted to $19\%$ (or a 3.5
fold relative increase, respectively). The lessreactive
DABCO precursors 16 and 17 furnished exclusively the
SN2ring-opening products. With regard to the counter ion,
less basicconditions appeared to be preferable, since 9 vs.
2 precursors gavehigher RCCs with triflate vs. bicarbonate
counter ion. The counter ionhad no impact on
radiofluorination of precursors bearing trimethy-lammonium
and DABCO-ammonium leaving groups.Conclusions: [ 18
F]Me4NF/X can be rapidly prepared by minimalistpreprocessing
and is considerably more reactive than commonly used[ 18
F]TEAF. In particular, [ 18 F]Me4NF/OTf is a promising
radiofluorina-tion agent, which afforded high RCCs for a
broad scope of radiolabelingprecursors.ReferenceLee et al.,
J. Org. Chem. 2021, 86, 14121–14130.},
month = {May},
date = {2023-05-22},
organization = {25th International Symposium on
Radiopharmaceutical Sciences, Honolulu
(USA), 22 May 2023 - 26 May 2023},
subtyp = {After Call},
cin = {INM-5},
cid = {I:(DE-Juel1)INM-5-20090406},
pnm = {5253 - Neuroimaging (POF4-525)},
pid = {G:(DE-HGF)POF4-5253},
typ = {PUB:(DE-HGF)6},
doi = {10.34734/FZJ-2024-03440},
url = {https://juser.fz-juelich.de/record/1026496},
}