A series of aripiprazole (AR3) syntheses were performed at laboratory scale (10 mmol of the ARI substrate) in order to optimize the amount of another substrate AR2, as well as Na2CO3, ethanol and varying the reaction time. The reaction parameters were chosen according to the D-optimal plans. A high conversion ratio, about 90-99%, was obtained. Purity of crude product (AR3) was determined by HPLC. Molar content of crude reaction product was predicted theoretically with the use of the mass balance and the corresponding HPLC parameters. The theoretical predictions were verified with the potentiometric and thermogravimetric analysis of selected samples. Based on the predicted molar content of reaction mixtures, a series of reaction response surfaces was calculated and optimal set of reaction parameters for aripiprazole synthesis was determined.