Many design variables and constraints, such as operating temperature and pressure of existing batch distillation or operating temperature of existing cooling and heating media, must be verified and satisfied during design and optimization when an existing batch distillation column is utilized for new mixture. The convergence of batch distillation simulation is sensitive with the initial values of these variables. Thus, a new systematic methodology was proposed to design and optimize separation of a new mixture using an existing batch column. The systematic methodology was based on an industrial case study of dichlorodifluoromethane (R-12) reclamation from a waste refrigerant mixture. Based on a comparison of the Pxy diagram with experimental data, “REFerence fluid PROPerties” was selected as the thermodynamic model. After design and optimization using shortcut and rigorous methodologies, the existing batch distillation unit was operated to validate the proposed methodology. The experimented performance match well with the simulated results. Under the optimized operating condition, complete purification of R-12 (purity=99.5%) was achieved experimentally after 28.3 h. The advantages and disadvantages of the proposed methodology were then discussed.