High Yielding Continuous-Flow Synthesis of Norketamine

Marcos Veguillas Hernando, Jonathan C. Moore, Rowena A. Howie, Richard A. Castledine, Samuel L. Bourne, Gareth N. Jenkins, Peter Licence, Martyn Poliakoff, Michael W. George

Research output: Journal PublicationArticlepeer-review

6 Citations (Scopus)


A new continuous-flow process is presented for synthesis of the pharmaceutical intermediate norketamine (5). Our approach has been to take the well-established and industrially applied batch synthetic route to this promising antidepressant precursor and convert it to a telescoped multi-stage continuous-flow platform. This involves the α-bromination of a ketone, an imination/rearrangement sequence with liquid ammonia, and a thermally induced α-iminol rearrangement. Our approach is high yielding and provides several processing advantages including the reduction of many of the hazards conventionally associated with this route, particularly in the handling of liquid bromine, hydrogen bromide gas, and liquid ammonia. Each of these presents serious operational challenges in a batch process at scale.

Original languageEnglish
Pages (from-to)1145-1151
Number of pages7
JournalOrganic Process Research and Development
Issue number4
Publication statusPublished - 15 Apr 2022
Externally publishedYes


  • bromination and amination
  • continuous manufacturing
  • norketamine

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Organic Chemistry


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