A Scalable Synthesis of the Antidepressant Agomelatine by a Tandem Allylic Chlorination-Isomerization Process

A concise, scalable, and industrially applicable process for the synthesis of the antidepressant agomelatine is described. The process relies on a tandem allylic chlorination–isomerization sequence, on a tetralone‐derived allyl carbinol, as the key transformation. The target compound is obtained in five steps from commercially available 7‐methoxy‐1‐tetralone, in 52.3 % overall yield after final recrystallization. A tandem allylic rearrangement–isomerization sequence on a tetralone‐derived allyl carbinol was applied for the preparation of agomelatine, a high‐potential antidepressant agent with improved pharmacokinetic profile. The active pharmaceutical ingredient (API) was obtained in 52.3 % overall yield and excellent purity (> 99.5 %) by a simple process amenable to industrial‐scale applications.