Use of dichloromethane for preparative supercritical fluid chromatographic enantioseparations

Preparative SFC is the technique of choice for small scale (mg to hundreds of grams) enantioseparations. Traditionally methanol, ethanol or isopropanol are used as a modifier for preparative SFC. When compounds being purified using preparative SFC exhibit poor solubility in carbon dioxide and these modifers, poor peak shape, low purification throughput, high solvent usage and potential sample precipitation and system blockage can occur. This paper discusses the use of dichlormethane as a modifier (alone or with other solvents) for analytical and preparative enantioseparations. It was shown that the use of dichloromethane as a modifier in preparative SFC can improve racemate solubility, leading to higher purification productivities and reduced solvent usage compared to traditional modifiers. Decreases in solvent consumption and decreased E factors were also realized. The applicability and advantages of this technique will be demonstrated during the preparative resolution of multiple enantiomers at the hundreds of gram scale.