Synthesis Of Arzoxifene

Arzoxifene is the third-generation selective estrogen receptor modulator, which was developed by Eli Lilly company after raloxifene, arzoxifene is mainly used for the prevention and treatment of osteoporosis and breast cancer.3-bromo-2-(4-bromophenyl)-6-methoxy benzo[b]thiophen sulfoxide was obtained from 4-bromoacetophenone via the bromination, condensation, cyclization, bromination and oxidation. Hydroquinone was performed via single-benzyl protection, condensation with 1, 2-dibromethane and piperidine in turn and hydrogenation-deprotection to provide the intermediate 4-[2-(1-piperidinyl)ethoxy]phenol. Finally, the condensation of 3-bromo-2-(4-bromophenyl)-6-methoxy benzo[b]thiophen sulfoxide and 4-[2-(1-piperidinyl)ethoxy] phenol gave the key intermediate 3-[4-[2-(1-piperidinyl)ethoxy]phenoxy]-6-methoxy-2-(4-bromophenyl)benzo[b]thiophene sulfoxide, from which the product arzoxifene was achieved via the reduction, demethylation and methoxylation in an overall yield of 24.3%(based on 4-bromoacetophenone).The structures of the intermediates and products were confirmed by1HNMR and MS spectra. Better technical parameters of synthesizing Arzoxifene were obtained from the discussion of factors of affecting the reactions above.