A simulation study of n-butyl acetate production with the [Hpy][HSO4] ionic liquid catalyst was performed. Due to the lack of phase equilibrium data, the binary interaction parameters of the NRTL model for ionic liquid and reactive species were calculated by the COSMO-RS technique. A reactive distillation process with recycled ionic liquid stream was proposed, and the column configuration was optimized by minimization of the total annual capital. The novel process is considerably efficient and economic compared to the traditional reactive distillation process of nonionic liquids. With the steady-state parameters, a plant-wide control structure was further developed to evaluate the robustness of the control system by exerting the disturbances of feed flow rate and feed composition. Dynamic simulation results suggest that the control scheme with a composition controller is timely and effective.