Formal Synthesis of Fesoterodine by Acid‐Facilitated Aromatic Alkylation

Abstract

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.

Evaluation of gem-Diacetates as Alternative Reagents for Enzymatic Regio- and Stereoselective Acylation of Alcohols

“…1 H NMR (400 MHz, CDCl 3 ) δ 7.36–7.24 (m, 5H), 4.94 (dd, J = 8.7, 3.8 Hz, 1H), 3.91–3.68 (m, 2H), 2.75 (s, 2H), 2.05–1.86 (m, 2H); 13 C­{ 1 H} NMR (100 MHz, CDCl 3 ) δ 144.3, 128.5, 127.5, 125.6, 74.2, 61.3, 40.4. The 1 H and 13 C­{ 1 H} NMR data were in accordance with those reported in the literature …”

“…The 1 H and 13 C{ 1 H} NMR data were in accordance with those reported in the literature. 48 Synthesis of rac-1-Phenyl-1,2-ethanediol. The suspension of styrene oxide (0.6 g, 5 mmol, 1.0 equiv) in distilled water (100 mL, 50 mM) was heated in an oil bath at 60 °C.…”