Gas antisolvent fractionation based optical resolution of ibuprofen with enantiopure phenylglycinol

Optical resolution is still the dominant route to obtaining enantiopure active ingredients. The traditional methods require large organic solvent quantities and long processing times. Antisolvent fractionation with supercritical carbon dioxide offers intensified processing by drastically reducing the time requirement of the diastereomeric salt precipitation. A novel optical resolution of ibuprofen was developed and optimized with phenylglycinol as a resolving agent and gas antisolvent fractionation as the separation method. Above the critical values of certain operational parameters (carbon dioxide to methanol ratio, apparent diastereomeric salt concentration, equilibration time, the relative volume of the extracting fluid) the selectivity was roughly constant, the optical resolution is robust. The scalemic mixtures were purified by repeated resolution and enantiomeric purities above 99% were reached in three consecutive steps.