Microscale HPLC Predicts Preparative Performance at Millionfold Scale

The use of microscale HPLC for piloting the large-scale preparative chromatographic resolution of the enantiomers of a chiral pharmaceutical intermediate is reported with an example of a millionfold scale-up from a 300 μm i.d. column to a 30 cm i.d column. Performance and productivity at scale are accurately predicted by the microscale approach, which consumes only a small fraction of the material typically used for conventional loading studies. These results suggest a great potential for use of microscale HPLC loading studies during early synthetic route investigations, when only a small amount of sample is typically available.