The time minimization (free-end-time problem) of the transesterification reaction in a semi-batch reactor was performed using successive quadratic programming (SQP) and the cubic spline interpolation method, and the numerical optimization result was Verified by experiment. The process constraints of the semi-batch reactor are the rate of temperature increase, the amount of ethylene glycol (EG) in the vapour phase las an indicator of the flooding of dimethyl terephthalate (DMT) and the concentration of side products (especially diethylene glycol (DEG)). The proposed optimal temperature trajectory was applied to the industrial process and reduced the reaction time of the transesterification from 150 to 110 min (about a 25% reduction), while satisfying the process constraints, such as the upper limit of the byproduct concentration, the rate of temperature increase and the flooding.