Chiral Resolution of Racemic Cyclopropanecarboxylic Acids in Supercritical Carbon Dioxide

The chiral resolution of two racemic cyclopropanecarboxylic acids with the resolving agents (S)-2-(N-benzylamino) butan-1-ol and (R)-1-phenylethanamine was investigated. The resolutions were based on diastereomer salt crystallization in supercritical carbon dioxide. Unreacted compounds were removed by an extraction step. Experiments were performed in a continuously stirred tank reactor and good enantioselectivities were obtained in a single step. Pressure, temperature, and density were found to strongly affect both the optical purity and the selectivity of the resolutions. The crystal structures of the formed diastereomer salts were also studied via X-ray diffraction.