Formal Synthesis of Fesoterodine by Acid-Facilitated Aromatic Alkylation

The competitive muscarinic receptor antagonist fesoterodine is a congener of tolterodine and has better efficiency compared to tolterodine. In this study, we present an efficient synthesis of the fesoterodine intermediate 3‐(3‐diisopropylamino‐1‐phenylpropyl)‐4‐hydroxybenzaldehyde from ethyl benzoylacetate by Friedel–Crafts alkylation in the presence of an acid as a key reaction step. The synthesis is carried out by the reduction of the ketoester to a 1,3‐diol, diisopropylamine substitution, and Friedel–Crafts alkylation, followed by reduction and chiral resolution.