A side‐reactor column (SRC) configuration, which integrates vacuum distillation with atmospheric reaction, was developed for dimethyl adipate (DMA) production. The sequential optimization method was applied to optimize the design parameters including side stream drawn stage, reactor numbers, and catalyst loading with total annual cost (TAC) as objective function in order to realize the economical design. The best economic performance was achieved as the result of the specific SRC configuration featuring one column with 20 stages where DMA was drawn from the 5th stage and one side‐reactor was equipped in the bottom. Moreover, a proportion‐temperature cascade control structure was successfully developed which avoids the disturbance of inlet flow rate and composition.