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 towards the -lactamase inhibitor vaborbactam. This includes the successful implementation of the continuous concept at a multi-ton 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.