Synthesis of the E and Z Isomers of the Antiestrogen Tamoxifen and Its Metabolite, Hydroxytamoxifen, in Tritium-Labeled Form

Both isomers of the potent antiestrogen tamoxifen (1,2-diphenyl-1-[4-[2-(dimethylamino)ethoxy]phenyl]-1-butene: E isomer = ICI-47699; Z isomer = ICI-46474, Nolvadex) and its metabolite, hydroxytamoxifen (1-[4-[2-(dimethylamino)ethoxy]phenyl]-1-(4-hydroxyphenyl)-2-phenyl-1-butene), have been synthesized in a high specific activity, tritium-labeled form by catalytic tritium-halogen exchange performed on brominated precursors. The synthesis of another precursor to labeled tamoxifen which would enable the incorporation of three tritium atoms into the molecule by tritium-halogen exchange is reported.