Carica papaya Lipase Catalysed Resolution of β‐Amino Esters for the Highly Enantioselective Synthesis of (S)‐Dapoxetine

摘要: An efficient synthesis of the (S)-3-amino-3-phenylpropanoic acid enantiomer has been achieved by Carica papaya lipase (CPL) catalysed enantioselective alcoholysis corresponding racemic N-protected 2,2,2-trifluoroethyl esters in an organic solvent. A high enantioselectivity (E > 200) was two strategies that involved engineering substrates and optimization reaction conditions. Based on resolution a series amino acids, it found structure substrate profound effect CPL-catalysed resolution. The rate were significantly enhanced switching conventional methyl ester to activated trifluoroethyl ester. When considering steric effects, substituted phenyl groups should not both be large for mechanism alcoholoysis acids is discussed delineate requirements Finally, scaled up, products separated obtained good yields (≥ 80 %). used as key chiral intermediate (S)-dapoxetine with very enantiomeric excess (> 99 %).