Preparation of tamoxifen

It has been a problem to prepare the anti-cancer drug Tamoxifen, of formula free of its geometric isomer E Tamoxifen. It has now been found that Tamoxifen can be prepared in a two-step reaction comprising (1) a McMurry olefin synthesis between propiophenone and a benzophenone substituted in the 4-position of one ring by a 2-haloethoxy group, to yield a Z(1,2-diphenyl-1-[4-(2-haloethoxy)-phenyl]-1-butene, which is then reacted with dimethylamine (with conservation of the Z geometric isomer in this reaction). The McMurry olefin synthesis involves a catalytic reduction involving a substantially zero-valent titanium species, which can be generated by titanium trichloride or tetrachloride and a powerful reducing agent.