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Synthesis of 6,6-Dimethyl-3-azabicyclo [3.1.0]hexane via Ru (II)-catalyzed intramolecular cyclopropanation

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Abstract

6,6-Dimethyl-3-azabicyclo[3.1.0]hexane (6,6-DMABH) is a crucial component in several antiviral medications, such as boceprevir and pf-07321332. To enable more efficient synthesis of 6,6-DMABH, we have developed an innovative approach that utilizes intramolecular cyclopropanation of alpha-diazoacetates via Ru (II) catalysis and the Gabriel synthesis. Gram-scale synthesis of 6,6-DMABH from 3-methyl-2-butenol is achieved in seven distinct steps, resulting in a total yield of 28%.

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Fig. 1
Scheme 1
Scheme 2

Data availability

The data that support the findings of this study are available in the supplementary material of this article.

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Acknowledgements

The authors are grateful for financial support provided by the ABA Chemicals Corporation.

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Authors and Affiliations

  1. School of Pharmacy, Nantong University, Nantong, 226001, China

    Yu Li, Yujie Ma, Shihao Cheng, Chenhu Dong, Xueer Zhong & Yu Zhao

  2. ABA Chemicals Corporation, Taicang, 215433, China

    Jun Xu

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  1. Yu Li
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  2. Yujie Ma
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Correspondence to Yu Zhao.

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Li, Y., Ma, Y., Cheng, S. et al. Synthesis of 6,6-Dimethyl-3-azabicyclo [3.1.0]hexane via Ru (II)-catalyzed intramolecular cyclopropanation. Med Chem Res 32, 2501–2504 (2023). https://doi.org/10.1007/s00044-023-03158-z

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