Scale-up is a topic of paramount importance in the industry, drawing on inputs from safety, economic, regulatory and efficiency perspectives. Never before has so much attention focussed on chemical synthesis and workflow. The topic of scale-up is diverse but at its fundamental level, aims to fashion economically viable outputs from simple lab techniques and exploration based on the solid ground of scientific first principles. On scale-up; we often switch evaporation for crystallization, convert overnight lab-scale ‘convenience’ reactions to more effective sequences, think about whether those heat and energy inputs are really necessary, risk assess for runaways etc but how should we handle purification?
For chemists performing bench-scale organic synthesis, flash column chromatography is often the primary purification technique. When synthesis needs scaling to multi-gram levels, so does the flash purification. The logical approach is to increase the flash cartridge or column size, but this is only part of the solution. In this article we discuss the process of simplifying flash purification scale-up.
Scaling-up flash chromatography can seem a daunting task but it is a fairly straightforward process once the following parameters are determined:
Chemists are often taught how to use glass columns in schools, so they take fundamental background experience into industry which provides an intuitive advantage in process development applications. However, with the exception analytical RP-HPLC, there is usually relatively little experience of preparative scale reversed phase purification.