RAPID SYNTHESIS OF N,N'-DISUBSTITUTED PIPERAZINES - APPLICATION TO THE PREPARATION OF NO CARRIER ADDED 1-(4-[18F]FLUOROPHENYL)PIPERAZINE AND OF AN [F-18] SELECTIVE LIGAND OF SEROTONINERGIC RECEPTORS (5HT2 ANTAGONIST)

An efficient and rapid method of piperazine formation (>50%, 30 min) involving the reaction of N,O,O'-tris(toluene-p-sulfonyl)bis(2-hydroxyethyl)amine 3 and 4-fluoroaniline in an alcohol or in hexamethylphosphoramide has been developed. It has been applied to the preparation of 1-(4-[F-18]fluorophenyl)piperazine 6b, a new precursor in [F-18]-labelling for positron emission tomography studies. Compound 6b was obtained in 7-15% decay corrected radiochemical yield in a synthesis time of 145-165 min counted from the labelled precursor [F-18]fluoride and a radiochemical purity greater than 98% after HPLC purification. The utility of 6b was demonstrated by the synthesis of the [F-18]naphthosultam 8b, a selective antagonist of 5-HT2 receptors. Compound 8b was obtained radiochemically pure in 50 min from 6b (including HPLC) and in an overall yield of 2.5-12% (decay corrected) from [F-18]fluoride.