The phase equilibrium of the n-butanol – n-butyl acetate – methyl isobutyl ketone system was studied using a computational experiment. To separate the mixture, an extractive distillation in the presence of various solvents: dimethyl sulfoxide, N-methyl-2-pyrrolidone and sulfolane was selected. The calculation of the vapor-liquid equilibrium of derivatives of quaternary systems (original ternary system + separating agent) was carried out and the difference in the change in the relative volatility of azeotrope-forming pairs of components in the presence of different solvents was shown. Two separation flowsheets with different structures were proposed. The columns operation parameters that ensure the production of substances of marketable quality with minimal energy consumption were determined. It was shown that the lowest energy consumption is observed for a flowsheet with dimethyl sulfoxide as the most selective agent.