A solvent‐free, chemoenzymatic reaction sequence for the enantioselective synthesis of β‐amino acid esters has been kinetically and thermodynamically characterized. The coupled sequence comprises a thermal aza‐Michael addition of cheap starting materials and a lipase catalyzed aminolysis for the kinetic resolution of the racemic ester. Excellent ee values of >99% were obtained for the β‐amino acid ester at 60% conversion. Kinetic constants for the aza‐Michael addition were obtained by straightforward numerical integration of second‐order rate equations and nonlinear fitting of the progress curves. A different strategy had to be devised for the biocatalytic reaction. Initially, a simplified Michaelis–Menten model including product inhibition was developed for the reaction running in THF as an organic solvent. Activity based parameters were used instead of concentrations in order to facilitate the transfer of the kinetic model to the solvent‐free system. Observed solvent effects not accounted for by the use of thermodynamic activities were incorporated into the kinetic model. Enzyme deactivation was observed to depend on the ratio of the applied substrates and also included in the kinetic model. The developed simple model is in very good agreement with the experimental data and allows the simulation and optimization of the solvent‐free process. Biotechnol. Bioeng. 2012; 109:1479–1489. © 2012 Wiley Periodicals, Inc. A solvent‐free, chemoenzymatic reaction sequence comprising a thermal aza‐Michael addition and a lipase catalyzed aminolysis for the enantioselective synthesis of β‐amino acid esters has been kinetically and thermodynamically characterized. Due to the added complexity of the enzyme catalyzed reaction in a solvent‐free system kinetic parameters were initially determined in an organic solvent and subsequently transferred to the solvent free system by applying a kinetic model based on thermodynamic activities.