Preparation of a pharmaceutical intermediate: An example of how inherent safety can be maximised during the early stages of process development

An inherently safe process has been defined as one which by virtue of its design will not generate a hazard if a fault occurs. Whilst inherent safety has traditionally been pursued by working with the principles of substitution, minimisation, attenuation and simplification 1, it is often very difficult, if not impossible, to make all processes inherently safe. In this situation the goal then becomes one of making the process as inherently safe as possible. The purpose of this paper is to show, by reference to the synthesis of a pharmaceutical intermediate, how it is possible to make very significant increases in the level of inherent safety within a process providing thermal stability and kinetic data is available.