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A Convenient 5-exo-dig Cyclization Route to Diastereomerically Pure Methyl (2S)-2-(1-benzyl-3-oxo-1,3-dihydro-2H-isoindol-2-yl)-3-methylbutanoate

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Chemistry of Heterocyclic Compounds Aims and scope

A robust method toward the synthesis of diastereomerically pure methyl (2S)-2-(1-benzyl-3-oxo-1,3-dihydro-2H-isoindol-2-yl)-3-methylbutanoate has been described. The key reactions in the synthesis are: HATU-mediated coupling, Pd-catalyzed Sonogashira coupling, base-mediated 5-exo-dig cyclization, and catalytic hydrogenation. The diastereomeric mixture is subjected to trituration with heptane to furnish both diastereomers in moderate yields. The relative stereochemistry was confirmed by the single crystal X-ray diffractometry. The key feature of the method is the simplicity of the diastereomeric separation.

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Authors and Affiliations

  1. Department of Chemistry, Galgotias University, Plot No. 2, Sector 17-A, Yamuna Expressway, Greater Noida, Uttar Pradesh, 201308, India

    Dnyaneshwar Nighot & Arvind Kumar Jain

  2. Department of Chemistry, University of Delhi, New Delhi, 110007, India

    Mandeep Singh

  3. Amity School of Applied Sciences, Amity University Haryana, Amity Education Valley, Gurugram, Haryana, 122413, India

    Varun Rawat

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  1. Dnyaneshwar Nighot
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  2. Arvind Kumar Jain
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Correspondence to Mandeep Singh or Varun Rawat.

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Published in Khimiya Geterotsiklicheskikh Soedinenii, 2020, 56(10), 1370–1374

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Nighot, D., Jain, A.K., Singh, M. et al. A Convenient 5-exo-dig Cyclization Route to Diastereomerically Pure Methyl (2S)-2-(1-benzyl-3-oxo-1,3-dihydro-2H-isoindol-2-yl)-3-methylbutanoate. Chem Heterocycl Comp 56, 1370–1374 (2020). https://doi.org/10.1007/s10593-020-02825-y

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