Continuous flow reactors have been used in the chemical industries for decades. They are often preferable to batch systems due to enhanced reproducibility and scalability, improved yields, and better control over processing conditions. While the pharmaceutical industry has traditionally employed batch reactors, many manufacturing processes are beginning to incorporate continuous flow reactors. Low volume, high throughput continuous flow reactors are especially suited for reactions containing high exotherms and/or dangerous starting materials.

Here we consider the challenges faced when converting a traditional batch process to a continuous flow system for the production of a pharmaceutical intermediate. The reaction of interest consumes diazomethane, a hazardous material, and also produces a temperature-sensitive intermediate. We examine the optimization process for this reaction involving size scale, flow rate, concentration, and temperature. Also, the inherent safety advantages of a continuous flow system for this type of reaction are discussed.