The invention discloses a preparation method of N-((1R,4R)-4-(4-(cyclopropylmethyl)piperazine-1-yl)cyclohexyl)acetamide. The preparation method comprises the following steps: (1) reacting a compound represented by the structural formula (2) and a compound represented by the structural formula (3) in a solvent in the presence of a catalyst namely tetraisopropyl titanate; (2) adding an alcoholic solvent and a reducing agent, carrying out reactions (time B) at a room temperature, and collecting N-((1R,4R)-4-(4-(cyclopropylmethyl)piperazine-1-yl)cyclohexyl)acetamide from the reaction products. The method adopts a one-pot method; the reaction product is the target product 4, the yield is high, and the reactions are controllable. The results of a large amount of experiments show that the high yield of target product 4 can be realized only the following conditions are met: one pot method is adopted, and tetraisopropyl titanate, alcohol, and reducing agent exist at the same time. The preparation method has the advantages that the raw materials are easily-available, the conditions are mild, the post treatment is simple, the yield of target product is high, and the preparation method is suitable for massive industrial production.