Application of n.c.a. 4-[18F] fluorophenol in diaryl ether syntheses of 2-(4-[18F] fluorophenoxy)-benzylamines

The availability of no-carrier-added (n.c.a.) 4-[F-18]fluorophenol offers the possibility of introducing the 4-[F-18]fluorophenoxy moiety into potential radiopharmaceuticals. Besides alkyl-aryl ether synthesis using n.c.a. 4-[F-18]fluorophenol the diaryl ether coupling is an attractive synthetic method to enlarge the spectrum of interesting labelling procedures. As examples the syntheses of n.c.a. 2-(4-[F-18]fluorophenoxy)-N,N-dimethylbenzylamine and n.c.a. 2-(4-[F-18]fluorophenoxy)-N-methylbenzylamine were realized by an Ullmann ether synthesis of corresponding 2-bromobenzoic acid amides using tetrakis(acetonitrile)copper(I) hexafluorophosphate as catalyst and a subsequent reduction of the amides formed. The radiochemical yield of the coupling varied between 5 and 65% based on labelled 4-[F-18]fluorophenol. Both compounds are structural analogues of recently published radiotracers for imaging the serotonin reuptake transporter sites (SERT). However, in vitro binding assays of both molecules showed only a low affinity towards monoamine transporters. Copyright (C) 2004 John Wiley Sons, Ltd.