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Development of a Continuous Flow Process for a Matteson Reaction: From Lab Scale to Full-Scale Production of a Pharmaceutical Intermediate

By Stueckler, Clemens; Hermsen, Peter; Ritzen, Bas; Vasiloiu, Maria; Poechlauer, Peter; Steinhofer, Stefan; Pelz, Andreas; Zinganell, Christopher; Felfer, Ulfried; Boyer, Serge; Goldbach, Michel; de Vries, André; Pabst, Thomas; Winkler, Georg; LaVopa, Vito; Hecker, Scott; Schuster, Christian

View Resource (DOI)

Category

Peer-reviewed journal

Published on CMKC

Abstract

Within this paper, we present the design, development, and scale-up of a process for a continuous Matteson reaction to produce a key intermediate toward the β-lactamase inhibitor vaborbactam. This includes the successful implementation of the continuous concept at a multiton production scale for the API at Patheon, part of Thermo Fisher Scientific. The first-generation continuous flow production with its discontinuous downstream processing was further developed to a fully continuous production through installation of a continuous loop reactor. This enabled increased productivity and energy efficiency, eliminated volume and time bottlenecks, and reduced waste.

Journal

Organic Process Research & Development. Volume 23, 2019, 1069-1077

DOI

10.1021/acs.oprd.8b00340

Type of publication

Peer-reviewed journal

Affiliations

  • Patheon Austria GmbH
  • InnoSyn B.V.
  • Qpex Biopharma, Inc.; Patheon Regensburg GmbH; Melinta Therapeutics

Article Classification

Research Article

Classification Areas

  • Intermediate
  • API

Tags

  1. API
  2. α-chloro-boronate
  3. continuous loop reactor
  4. Intermediate
  5. β-lactamase inhibitor
  6. Matteson Reaction
  7. Research Article
  8. Scale-up
  9. vaborbactam