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

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Abstract

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.

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Authors and Affiliations

  1. Fujian University of Traditional Chinese Medicine, Fujian, China

    Yi Lu & Xueqing Zhao

  2. Fujian Institute of Microbiology, Fujian, China

    Yangwei Huang, Zhong Chen & Yanqing Lin

Authors
  1. Yi Lu
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  2. Yangwei Huang
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  3. Zhong Chen
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  4. Yanqing Lin
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  5. Xueqing Zhao
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Correspondence to Xueqing Zhao.

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Lu, Y., Huang, Y., Chen, Z. et al. A new process for the synthesis of nafoxidene as a key intermediate of lasofoxifene. Res Chem Intermed 41, 6051–6056 (2015). https://doi.org/10.1007/s11164-014-1721-7

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  • DOI: https://doi.org/10.1007/s11164-014-1721-7

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