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Chemistry of Heterocyclic Compounds

, Volume 55, Issue 4–5, pp 421–434 | Cite as

Expanding the chemical space of sp3-enriched 4,5-disubstituted oxazoles via synthesis of novel building blocks

  • Evgeniy Y. Slobodyanyuk
  • Andrii A. Andriienko
  • Bohdan V. Vashchenko
  • Dmitriy M. Volochnyuk
  • Sergey V. Ryabukhin
  • Oleksandr O. GrygorenkoEmail author
Article
  • 8 Downloads

An efficient approach to the preparation of novel sp3-enriched 4,5-disubstituted oxazoles bearing a functional group at the C-4 position is described. The method commenced with synthesis of ethyl oxazole-4-carboxylates (13 examples, 63–99% yield), with subsequent function insertion to the heterocyclic core by late-stage functional group transformation. The LiBH4-mediated reduction of ethyl oxazole-4-carboxylates was the only method which could be optimized at multigram scale (up to 40 g), and its scope was demonstrated by preparation of 13 alcohols with (cyclo)alkyl, fluoroalkyl, or N-Boc-aminoalkyl moiety at the C-5 position (47–89% yield). The utility of these key intermediates was demonstrated by the preparation of chlorides (13 examples, 90–99% yield), azides (13 examples, 83–99% yield), amines (13 examples, 80–98% yield), and sulfonyl chlorides (4 examples, 68–97% yield) – advanced building blocks for synthetic and medicinal chemistry.

Keywords

alcohols amines azides chlorides esters oxazoles sulfonyl chlorides building blocks 

Supplementary material

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Evgeniy Y. Slobodyanyuk
    • 1
    • 2
  • Andrii A. Andriienko
    • 1
    • 3
  • Bohdan V. Vashchenko
    • 1
    • 3
  • Dmitriy M. Volochnyuk
    • 2
  • Sergey V. Ryabukhin
    • 3
  • Oleksandr O. Grygorenko
    • 1
    • 3
    Email author
  1. 1.Enamine Ltd.KyivUkraine
  2. 2.Institute of Organic ChemistryNational Academy of Sciences of UkraineKyivUkraine
  3. 3.Taras Shevchenko National University of KyivKyivUkraine

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