Diastereomer salt formation of ibuprofen in supercritical carbon dioxide

The first in situ diastereomeric salt formation reaction in supercritical carbon dioxide is reported in this paper. The reaction studied was the salt formation between racemic ibuprofen and (R)-(1)-phenylethylamine, and was combined with supercritical fluid extraction in order to separate the unreacted enantiomers from the formed salts. The effects of pressure, temperature and reaction time were studied in detail. With increasing pressure, the reaction rate and the resolution efficiency at equilibrium increase. With increasing temperature, the optical purity of ibuprofen in the carbon dioxide phase increases, as does the reaction rate.