An Improved Scalable Route to Pure Dronedarone Hydrochloride

Abstract

An efficient scalable synthesis for dronedarone hydrochloride (2) via Friedel−Craft acylation of 2-(-2-butyl-1benzofuran-5-yl)-1H-isoindole-1,3(2H)dione ( 12) with 4-(3-chloropropoxy) benzoic acid (13) in good yield and high purity has been developed by using Eaton's reagent instead of hazardous and toxic metal halide catalyst like AlCl 3 or SnCl 4 .

Convergent Synthesis of Dronedarone, an Antiarrhythmic Agent

“…Several other synthetic routes of 2 also depended on the use of benzo[b] furan 3, and minor improvements of reaction conditions and the exchange of steps have been reported. [8][9][10][11][12][13] From a drug-discovery point of view, those processes lack the flexibility of the 2-position in benzo [b] furan because this position was defined at the first stage of the synthesis. Therefore, an alternative route toward 2 that contains the introduction of a variety of substituents at the 2-position on benzo[b] furan at later stage was needed.…”

Synthesis and characterization of new related substances of the antiarrhythmic drug dronedarone hydrochloride

“…Most of the synthetic processes for preparing Dronedarone Hydrochloride use the cost-contributing intermediate (3) as starting material [6][7][8]. Briefly, phenol 3 is alkylated with 1-chloro-3-di-n butylaminopropane hydrochloride (4) and the resulting intermediate aniline derivative, isolated as dioxalate salt 6, is treated with methanesulfonyl chloride to yield Dronedarone free base that is subsequently isolated as the hydrochloride salt 1 (Fig.…”