Direct uncatalyzed amination of 2-chloropyridine using a flow reactor

  • Hamper B
  • Tesfu E
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Chloropyridines are efficiently converted into 2-amino-pyridines by uncatalyzed nucleophilic aromatic substitution (SNAr) in NMP using, a continuous-flow reactor. A variety of secondary amines undergo SNAr with both electron-rich and electron-deficient 2-chloropyridines to afford 2-aminopyridines in good to excellent yield. The flow reactor, which provides a short reaction time and high temperatures tip to 300 degrees C, can overcome the activation barrier for reactions with unactivated substrates. Short reaction times result in fewer side products and can afford milligram to multigram quantities of product using continuous flow.

Author-supplied keywords

  • Amination
  • Flow synthesis
  • Microflow reactor
  • Nucleophilic aromatic substitution

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  • Bruce C. Hamper

  • Eden Tesfu

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