Fast further purification of diastereomeric salts of a nonracemic acid by gas antisolvent fractionation

Abstract

A novel, green possibility of the further purification of the diastereomeric salt of 4-chloromandelic acid and 1-phenylethane-1-amine was developed. Gas antisolvent method using supercritical carbon dioxide was applied for the first time to precipitate the diastereomeric salts with increased purity followed by the supercritical fluid extraction of the dissolved diastereomers. The RR-salt can be purified to >99%, while fractionation-based purification of the SR-salt is limited to ~80%. The limiting initial diastereomeric excess correlates strongly with the atmospheric melting eutectic composition of the same salts, which suggests that despite the fast precipitation, the diastereomeric excess of the solid product is not kinetically determined. The efficiency of the diastereomeric enrichment is in the same range as that of the atmospheric reference experiments; however, technological advantages provided by the antisolvent precipitation method such as fast processing and dry product obtained suggest that this novel procedure is a promising alternative to the atmospheric methods.

A fast, new method to enhance the enantiomeric purity of non-racemic mixtures: self-disproportionation of enantiomers in the gas antisolvent fractionation of chlorine-substituted mandelic acid derivatives

“…A solution containing approx. 100 mg of the acid investigated was filled into a 37 mL laboratory autoclave that was described in a previous communication 29 . The autoclave was tempered at 40 °C and pressurized with a known amount of supercritical carbon dioxide using a Teledyne ISCO 260D syringe pump to 16 MPa.…”

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.…”

Gas Antisolvent Fractionation: A New Approach for the Optical Resolution of 4-chloromandelic Acid

“…Carbon dioxide-involving experiments have even been conducted using the supercritical fluid as an antisolvent and as a reaction medium in diastereomeric salt formation as well [14][15][16][17][18][19]. Antisolvent methods have been studied in the production of enantiomerically pure compounds too [6,14,[20][21][22]. Also, supercritical carbon dioxide was used as the reaction medium of enzymatic kinetic resolutions [23].…”