Continuous Flow Reactors for Benign Production of Pharmaceuticals and Pharmaceutical Intermediates

The Meerwein-Ponndorf-Verley (MPV) reduction serves as an example of the advantages of the continuous flow reactors over batch reactors for pharmaceuticals and pharmaceutical intermediates. The MPV reduction is commonly used in the production of pharmaceutical intermediates, such as those used for HIV protease inhibitors. This is the first time MPV reduction reactions were carried out in a Corning® glass continuous flow reactor, specially-designed with multiple mixing structures and reaction zones to increase residence time, heat transfer and mass transfer. The glass reactor offers nonreactivity and corrosion resistance over a wide range of temperature (-25oC to 200oC) and pressure (up to 18 bar), which conventional steel reactors do not allow. Continuous flow reactors also allow a simplified approach to bulk production by scaling out as opposed to scaling up. The traditional MPV reduction protocol (Al(OiPr)3 in isopropanol) was modified to enable the technological transfer from batch to continuous mode. As a result, the MPV reduction of a model compound, benzaldehyde, ran with less catalyst in a substantially shorter time. These results are being used to develop a technology roadmap for the pharmaceutical industry to implement continuous flow processes in their manufacturing operations.