Optimization of automated flash chromatography methods for purification of two organic chemistry compounds for production use

Abstract

The present study aimed to optimize the purification method of two synthesis intermediates using an automated flash chromatography system, CombiFlash EZPrep. The main parameters to be optimized in the chromatography methods were the solid phase, the mobile phase, its gradient, sample handling, and the loading method. Thin layer chromatography (TLC) was used to optimize the mobile phase for effective compound separation and to verify the separated fractions. Following the optimization of the purification processes, productionscale purifications were conducted using the developed methods.

The objectives were to use less harmful solvents for health and the environment and to minimize the solvent consumption, and waste generated during the purification processes. While the primary objective was to achieve high product purity and yield, the objectives related to the reagent consumption could not be achieved. Nevertheless, working with the equipment reduces health risks and the active working time compared to the manual methods previously used. Furthermore, the data generated by the equipment provided informative data about the separation of compounds, enabling better data storage and traceability of purification runs.