Application of Flow and Biocatalytic Transaminase Technology for the Synthesis of a 1-Oxa-8-azaspiro [4.5] decan-3-amine

Added on:
10 Aug, 2021

Spirocyclic ring systems are useful intermediates in the design and synthesis of medicinally active agents and commonly found as cores in natural products. Recently, syntheses of a key intermediate Boc-protected-1-oxa-8-azaspiro[4.5]decan-3-amine 1 were examined. While multigram quantities of the racemic material could be made from the reduction of an energic azide intermediate, larger scale reactions and a chiral synthesis required further investigations. Herein, we describe the use of a continuous three-step flow process to scale the formation and reduction of an azide intermediate, and the use of a transaminase to prepare the desired enantiomer in high yield and enantiomeric excess.

  • Jeffrey T. Kohrta
  • Peter H. Dorffa
  • Michael Burnsb
  • Chewah Leeb
  • Steven V. O’Neilb
  • Robert J. Maguireb
  • Rajesh Kumarb
  • Melissa Wagenaarb
  • Loren Pricea
  • Manjinder S. Lalla
  • aMedicine Design, Pfizer Inc., 445 Eastern Point Road, Groton, Connecticut 06340, United States
  • bChemical Research and Development, Pfizer Inc., 445 Eastern Point Road, Groton, Connecticut 06340, United States
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