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

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.

Analysis of the Mechanism of Cholesterol Particle Formation by Liquid Antisolvent Crystallization

“…The antisolvent can be in the form of a supercritical fluid (SCF), such as supercritical carbon dioxide (ScCO 2 ), or a gas such as CO 2 , − or a liquid such as water . The general principles and fundamentals of particle engineering using supercritical fluids, and their diverse applications have also been reviewed comprehensively by Tabernero et al Specific applications of gas antisolvent (GAS) processes in the domain have also been presented by Elvassore et al and Zodge et al, while those of the supercritical fluid antisolvent (SAS) have been reviewed by Reverchon et al and Franco and De Marco …”

Model Building on Selectivity of Gas Antisolvent Fractionation Method Using the Solubility Parameter

“…While for typical GAS applications the goal is to completely precipitate the solute in a desired size, crystallization habit and morphology, gas antisolvent fractionation (GASF) is a combination of the precipitation and an extraction step [5,6]. The GASF technique can be efficiently used in diastereomeric salt based optical resolutions [7][8][9][10][11] and purification of scalemic mixtures as well [7,12,13]. However, the efficiency of GASF is influenced by various operational parameters.…”