Ethanol → N-(2-phenyl-pyridin-3-yl)-acetamide hydrochloride

Participants

Reaction Steps

To a mixture of N-(2-chloro-pyridin-3-yl)-acetamide (50,0 g, 29.3 mmol), phenylboronic acid (39.3 g, 32.2 mmol), sodium carbonate (49.7 g, 46.9 mmol), in toluene (400 mL), ethanol (100 mL), and water (200 mL) was added tetrakis(triphenylphosphine)palladium(0) (1.02 g, 0.883 mmol). The reaction mixture was heated to reflux for 8 hours, cooled to room temperature, and the layers were separated. The aqueous layer was extracted with ethyl acetate (500 mL) and the organic extracts were combined and concentrated to a yellow solid. The crude solid was dissolved in methanol (500 mL) and concentrated hydrochloric acid was added (10 mL). The solution was concentrated to a low volume and tetrahydrofuran (500 mL) was added. The solid was triturated, filtered and dried to afford N-(2-phenyl-pyridin-3-yl)-acetamide hydrochloride (62.5 g, 86%). M. p.=262-263° C. 1H NMR (300 MHz, DMSOd6) δ2.52 (s, 3), 6.30 (bs, 2), 7.64-7.72 (m, 6), 7.78 (dd, 1, J=1.2, 8.6), 8.06 (dd, 1, J=1.2, 5.2)

Provenance & Evidence