Piperidin-4-ol → 2'-(4-Methoxybenzyloxy)-4'-methyl-3,4,5,6-tetrahydro-2H-[1,3']bipyridinyl-4-ol

Participants

Reaction Steps

A mixture of 3-bromo-2-(4-methoxybenzyloxy)-4-methylpyridine (6.40 g, 20.77 mmol), 4-hydroxypiperidine (3.15 g, 31.15 mmol), tris(dibenzylideneacetone)dipalladium (761 mg, 0.831 mmol), racemic-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (1.03 g, 1.66 mmol), and sodium-t-butoxide (2.79 g, 29.08 mmol) in anhydrous toluene (200 ml) was heated at reflux under nitrogen for 22 hours. Upon cooling to room temperature, the reaction mixture was filtered through celite and the filtrate was diluted with ethyl acetate, washed with sat'd NaCl(aq.), dried (MgSO4), filtered, and concentrated. Elution through a flash column (silica gel 60, 230-400 mesh, 1:1 hexanes: EtOAc) gave the title compound as a black, viscous oil (4.76 g, 70%).

Provenance & Evidence