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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

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.