Design and operation of a filter reactor for continuous production of a selected pharmaceutical intermediate

Kim Müller Christensen, Michael Jønch Pedersen, Kim Dam-Johansen, Thomas Lønberg Holm, Tommy Skovby, Søren Kiil

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

A novel filter reactor system for continuous production of selected pharmaceutical intermediates is presented and experimentally verified. The filter reactor system consists of a mixed flow reactor equipped with a bottom filter, to retain solid reactant particles, followed by a conventional plug flow reactor, where residual reactant is converted by titration. A chemical case study, production of the pharmaceutical intermediate allylcarbinol by a reaction between allylmagnesium chloride and 2-chloro-thioxanthone, in the presence of a side reaction is considered. The synthesis is conducted in tetrahydrofuran solvent. The use of the filter reactor design was explored by examining the transferability of a synthesis step in a present full-scale semi-batch pharmaceutical production into continuous processing. The main advantages of the new continuous minireactor system, compared to the conventional semi-batch operation, are reduced impurity formation and the use of much lower reactor volumes (factor of 1000 based on the laboratory reactor) and less solvent consumption (from 5.8 to 2.3L/kg reactant). Added challenges include handling of continuous solid powder feeding, stable pumping of reactive slurries, and a possibility of continuous control.
Original languageEnglish
JournalChemical Engineering Science
Volume71
Pages (from-to)111-117
ISSN0009-2509
DOIs
Publication statusPublished - 2012

Keywords

  • Continuous design
  • Chemical reactors
  • Batch
  • Pharmaceuticals
  • Grignard
  • Optimization

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