Convergent Synthesis of Dronedarone, an Antiarrhythmic Agent

Abstract

We have developed a convergent synthesis of dronedarone, an antiarrhythmic agent. The key steps of the process are the construction of a benzofuran skeleton by iodocyclization and the carbonylative Suzuki-Miyaura cross-coupling for biaryl ketone formation. This synthetic route required only eight steps from 2-amino-4-nitrophenol in 23% overall yield.

Shielding Effect of Nanomicelles: Stable and Catalytically Active Oxidizable Pd(0) Nanoparticle Catalyst Compatible for Cross-Couplings of Water-Sensitive Acid Chlorides in Water

“…Because of the facile transmetalation of arylboronic acids to PS-750-M-stabilized Pd NPs, our evaluation on the catalytic activity of these Pd(0) NPs started with the cross-couplings of acid chlorides and boronic acids, providing access to functionalized ketones under mild aqueous conditions. − Recognizing the widespread distribution of these compounds in pharmaceuticals, agrochemicals, and fine chemicals, − this transformation could be a greener alternative compared to the traditional multistep route involving Grignard addition to an aldehyde followed by oxidation of the resulting alcohol. , Therefore, we investigated the possibility of such a C–C coupling reaction catalyzed by phosphine-free Pd(0) NPs using benzoyl chloride ( 1 ) and 4-(trifluoromethyl)­phenylboronic acid ( 2 ) as benchmark substrates under aqueous micellar conditions.…”

11C-Labeling of Aryl Ketones as Candidate Histamine Subtype-3 Receptor PET Radioligands through Pd(0)-Mediated 11C-Carbonylative Coupling

“…m.p. : 84–86 °C [ 27 ]). 1 H-NMR (DMSO- d 6 ) δ 11.96 (br s, 1H), 8.51 (d, J = 2.76 Hz, 1H), 8.15 (dd, J 1 = 8.98 Hz, J 2 = 2.78 Hz, 1H), 7.02 (d, J = 9.00 Hz, 1H).…”

Scalable α-Arylation of Nitriles in Aqueous Micelles using Ultrasmall Pd Nanoparticles: Surprising Formation of Carbanions in Water

“…Another important feature of the micellar catalysis with the aqueous PS-750-M is the higher solubility of oxygen in the interfacial region, which allows molecular oxygen to be used in the reaction pathway depicted in Scheme a to generate diarylketones, which are highly important drug molecules in medicinal chemistry as many drug molecules contain biaryl ketones. , In a one-pot process, after the completion of the α-arylation, we exposed the same reaction mixture to an oxygen atmosphere to obtain biaryl ketones 43 – 45 in good isolated yields.…”