A new process for the synthesis of nafoxidene as a key intermediate of lasofoxifene

作者：Lu Yi; Huang Yangwei; Chen Zhong; Lin Yanqing; Zhao Xueqing^*

来源：Research on Chemical Intermediates, 2015, 41(9): 6051-6056.

DOI：10.1007/s11164-014-1721-7

• Lasofoxifene
• Nafoxidene
• Synthesis
• Pinacol rearrangement

A novel brief process for the synthesis of nafoxidene has been developed. The epoxidation of 6-methoxy-1-{4-[2-(pyrrolin-1-yl)ethoxy)]phenyl}-3,4-dihydronaphthalene by m-CPBA directly gave the ketone 6-methoxy-1-[4-(2-(pyrrolidin-1-yl)ethoxy) phenyl]-3,4-dihydronaphthalen-2(1H)-one, which was subject to phenyl magnesium bromide/cerium chloride and subsequently treated with an acid to yield nafoxidene. In addition, the preparation of the starting naphthalene was also optimized by replacing the aromatic lithium at low temperature with its Grignard reagent at refluxing THF. This mild process, without the use of toxic or noble metals, was more cost-efficient and easily worked up.

• 出版日期2015-9
• 单位福建省微生物研究所; 福建中医药大学