Process improvement on the synthesis of atomoxetine

Atomoxetine is a highly selective norepinephrine reuptake inhibitor. Based on the analysis of the literature methods, the synthesis process of atomoxetine was improved. Using 3-chloropropiophenone-1 as the raw material, optically pure target product was obtained by asymmetric reduction, Mitsunobu reaction and condensation reaction in three steps, with a total yield of 26%. The third-step methylation sealing operation was changed to the reaction under normal pressure, which increased the feasibility of industrialization. The improved process operation was simplified and the reaction conditions were mild, which would provide a new method for the preparation of atomoxetine.