Kinetic resolution of 4-phenyl-2-azetidinone in supercritical carbon dioxide

The lipase-catalysed kinetic resolution of rac-4-phenyl-2-azetidinone was investigated in supercritical carbon dioxide (scCO2). Water (0.5mol equivalent) was used as nucleophilic donor. The effects of pressure and temperature were studied in a batch reactor (internal volume: 30mL). The optimum pressure and temperature of the β-lactam ring-opening reaction proved to be 14MPa and 70°C. Under optimum conditions, full conversion was achieved in 120h. The resulting (R)-β-phenylalanine (ee≥98%) and (S)-4-phenyl-2-azetidinone (ee≥99%) could be easily separated by scCO2 extraction of the (S)-β-lactam and subsequent washing of the enzyme with hot water to recover the amino acid.