Fast and reliable method for the preparation of ortho- and para-[18F]fluorobenzyl halide derivatives: Key intermediates for the preparation of no-carrier-added PET aromatic radiopharmaceuticals

Autor: Alain Plenevaux, Xavier Franci, Joël Aerts, Lionel Libert, Christian Lemaire, André Luxen
Rok vydání: 2012
Předmět:
Zdroj: Journal of Fluorine Chemistry. 138:48-55
ISSN: 0022-1139
Popis: A fast and reliable method suitable for the automated preparation of (substituted) [ 18 F]fluorobenzyl halides from several [ 18 F]fluorobenzaldehydes was developed. Aromatic nucleophilic substitution of trimethylammonium benzaldehyde triflate and nitro precursors was realized with no-carrier-added [ 18 F]fluoride. After labeling, fluorine-18 containing aldehydes were trapped on a Solid Phase Extraction (SPE) cartridge and the subsequent conversion into benzyl halide was directly realized, on-line, on the support. Reduction of the aldehydes (>95%) was near-quantitative with an aqueous solution of NaBH 4 . Halogenation was performed on the same support with different aqueous solutions of concentrated acid (HI, HBr, HCl). The conversion of benzyl alcohols into [ 18 F]fluorobenzyl halides (X = Cl, Br, I) usually proceeded within 2 min at high yields. The halogenation proceeded at room temperature, with the exception of the 2-[ 18 F]fluoro-3-methoxybenzyl, 2- and 4-[ 18 F]fluorobenzyl halides, which required the use of HBr/HOAc (33%). With this method, various [ 18 F]fluorobenzyl chloride, bromide and iodide compounds were obtained with high radiochemical purities (>90%) and with overall radiochemical yields of 15–70%. The radiosynthesis was completed in 30 or 45 min from EOB, starting from the ammonium or nitro precursor, respectively. By using the same solid support, 2- and 4-[ 18 F]fluorobenzyl bromide and iodide derivatives were near-quantitatively converted (>95%) into the corresponding azido compounds (60 °C, 5 min). As the reduction and halogenation steps were performed on solid supports, automation of the whole synthesis was straightforward.
Databáze: OpenAIRE