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 (0.5 mol equivalent) was used as nucleophilic donor. The effects of pressure and temperature were studied in a batch reactor (internal volume: 30 mL). The optimum pressure and temperature of the β-lactam ring-opening reaction proved to be 14 MPa and 70 °C. Under optimum conditions, full conversion was achieved in 120 h. 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.