Application of supercritical fluid extraction for fractionation of enantiomers

A novel, organic solvent free procedure was developed for separation of enantiomers of a racemate. Partial diastereomeric complex formation of trans-2-chloro-cyclohexan-1-ol and O,O′-dibenzoyl-(2R,3R)-tartaric acid monohydrate was performed in the melt of the alcohol. The highest resolution effiency was achieved, when the unreacted alcohol (R,R-enantiomer, e.e.=43.5%, yield=45.3%) was extracted with supercritical carbon dioxide at mild conditions (100 bar, 33 °C). Then in a second step the diastereomeric complex was in situ decomposed in the extractor (200 bar, 73 °C) and the S,S-enantiomer (e.e.=61.6%, yield=31.9%) was also extracted. These results are much better than those achieved by conventional methods. Decomposition temperature of the complex (73 °C) was much lower than that at atmospheric pressure (>100 °C), which indicates a great advantage of the supercritical conditions. The raffinate of the fractionated extraction was reused for new resolutions without further treatment. Effects of the amount of resolving agent and extraction pressure and temperature of the first extraction step were studied in details.