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Syntheses of meta-[18F]fluorobenzaldehyde and meta-[18F]fluorobenzylbromide from phenyl(3-Formylphenyl) iodonium salt precursors

Authors

  • Falguni Basuli,

    1. Imaging Probe Development Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Rockville, MD 20850, USA
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  • Haitao Wu,

    1. Imaging Probe Development Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Rockville, MD 20850, USA
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  • Gary L. Griffiths

    Corresponding author
    1. Imaging Probe Development Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Rockville, MD 20850, USA
    • Imaging Probe Development Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Rockville, MD 20850, USA
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  • This article is a US Government work and is in the public domain in the USA.

Abstract

18F-labeled fluorobenzaldehydes and fluorobenzylbromides are useful synthons for the preparation of positron emission tomography radiopharmaceuticals. Although ortho- and para-[18F]fluorobenzaldehydes can easily be prepared with high yields, the corresponding meta-derivatives are more problematic. In order to improve the yield of meta-[18F]fluorobenzaldehyde, we used the corresponding diaryliodonium salt precursors, since diaryliodonium salts had already been used as precursors in the preparations of 18F-labeled electron-rich, as well as electron-deficient, aromatic rings. Diaryliodonium salts with different counter ions [PhIPhCHO]X (X = Cl, Br, OTs, OTf) were synthesized. 18F radiolabeling was performed using different bases at different temperatures in the presence of a radical scavenger, 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO). The best conversion (∼80%) to meta-[18F]fluorobenzaldehyde was obtained using CsHCO3 base at a reaction temperature of 110°C. To study iodonium salt counter ion effects on radiofluorination, each precursor was separately treated with Cs[18F]F/CsHCO3 in DMF at 110°C for 5 min in the presence of TEMPO. Our observed reactivity order was OTs<Cl<OTf<Br. Meta-[18F]fluorobenzaldehyde thus obtained was reduced to the corresponding alcohol with aqueous NaBH4 at room temperature and then converted to meta-[18F]fluorobenzylbromide using triphenylphosphine dibromide. Formation of meta-[18F]fluorobenzylbromide was confirmed using high-performance liquid chromatography and the desired product was purified on a silica Sep-Pak® plus cartridge. Published in 2011 by John Wiley & Sons, Ltd.

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