The effect of water on the large-scale supercritical fluid chromatography purification of two factor XIa active pharmaceutical ingredients

•An SFC method exploiting water and ammonia as additives in both the mobile phase and sample solution was developed to accomplish purification and desalting (i.e. removing TFA) of each of the two zwitterionic APIs in one step.•A robust chiral SFC process using methanol-acetonitrile as modifier in CO2 was established to achieve a consistent operation, resolving >230 g of the racemic penultimate of BMS-962212.