Study On Laboratory Scale Process Of Raloxifene

• Main Authors: Jia-Shyang Yang, 楊佳雄
• Other Authors: Chi-Phi Wu
• Format: Others
• Language: zh-TW
• Published: 2002
• Online Access: http://ndltd.ncl.edu.tw/handle/vw6qzy

碩士 === 中原大學 === 化學研究所 === 90 === 3-methoxybenzenethiol is used as the starting material to yield Raloxifene. α-(3-methoxyphenylthio)-4-methoxyacetophenoe was prepared from the reaction of 3-methoxybenzenethiol with 2-bromo-4-methoxy acetophenone. The key intermediate 6-methoxy-2-(4-methoxyphenyl) benzo[b]thiophene was prepared by the cyclization rearrangement induced by polyphosphoric acid (PPA). The intermediate 4-(2-piperidinoethoxy)benzoic acid hydrochloride was prepared from the reaction of methyl-4-hydroxybenzoate with 1-(2-chloroethyl) piperidine hydrochloride. They reacted with 6-methoxy-2-(4-methoxyphenyl) benzo[b]thiophene to yield 6-hydroxy-2-(4-hydroxypheneyl)-3-[4-(2- piperidinoethoxyl)benzyl]benzo[b]thiophene hydrochloride (Raloxifene). The compoud 6-trimethylsiloxy-2-(4-trimethylsiloxyphenyl)benzo[b] thiophene 6-methoxy-2-(4-methoxyphenyl)benzo[b]thiophene was prepared from Bis-(N,N-trimethylsilyl)-urea (BSU ). It reacted with 4- (2-piperidinoethoxy)benzoic acid hydrochloride to yield Raloxifene. The latter method gave more efficient demethylation and environmental problems .