Gas Antisolvent Approach for the Precipitation of α-Methoxyphenylacetic Acid – (R)-1-Cyclohexylethylamine Diastereomeric Salt

A. Zodge, M. Kőrösi, M. T. , J. Madarász, I. Miklós Szilágyi, T. Sohajda and E. Székely

Abstract
One of the major drawbacks of diastereomeric salt precipitation based enantioseparation is the time and solvent requirement of crystallization. In the gas antisolvent (GAS) approach, supercritical carbon dioxide is applied as an antisolvent, and the precipitation takes place in a couple of minutes. By setting the process parameters diastereomeric excess, yields, and selectivity can be controlled. Applicability of the process is demonstrated on the resolution of racemic 2-methoxyphenylacetic acid with enantiopure (R)-(−)-1-cyclohexylethylamine. Diastereomeric excess values over 55 % along with 80 % yields were achieved at optimal conditions in a single step. (This work is licensed under a Creative Commons Attribution 4.0 International License.)

This work is licensed under a Creative Commons Attribution 4.0 International License

Keywords
supercritical CO2, optical resolution, α-methoxyphenylacetic acid, capillary electrophoresis