N.C.A. 18F-labelled norephedrine derivatives via α-aminopropiophenones

Article abstract of DOI:10.1002/1099-1344(200012)43:14<1345::AID-JLCR424>3.0.CO;2-N

N-protected 2-amino-1-([¹⁸F]fluorophenyl)-1-propanones are interesting fluorine-18 labelled intermediates to synthesize potential PET-tracers for mapping the adrenergic nervous system of the heart. Several N-protected α-aminoalkylarylketones were prepared to examine the direct nucleophilic n.c.a. ¹⁸F-fluorination of these carbonyl activated precursors. The influence of different protecting groups, the kind of leaving group and the stereoselective reduction of the keto function have been investigated in order to optimize the radiotracer production. It was shown that the ¹⁸F-substitution of the para-trimethylammonium group, e.g. of N-dibenzylated propiophenone, leads to radiochemical yields of up to 60%. The stereoselective reduction of the carbonyl function with formation of the n.c.a. erythro 2-N,N-dibenzylamino-1-(4-[¹⁸F]fluorophenyl)-1-propanol was performed using BH₃·THF. The diastereomeric excess was about 80%. Hydrogenolytical debenzylation was achieved with ammonium formiate in presence of palladium on charcoal to give the 4-[¹⁸F]fluoronorephedrine with a radiochemical yield of 15-20% within a total time of 60 min.