Br[C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1.[CH2:8]([O:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[OH:17])[CH3:9].CC(C)(C(=O)CC(=O)C(C)(C)C)C.C(=O)([O-])[O-].[Cs+].[Cs+].Cl.[OH-].[NH4+]>[Cu]Cl.C(OCC)(=O)C.C1(C)C=CC=CC=1>[CH2:8]([O:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[O:17][C:2]1[CH:3]=[N:4][CH:5]=[CH:6][CH:7]=1)[CH3:9]3-Bromopyridine (224 g, 1.42 mol) and 2-ethoxyphenol (275 g, 1.99 mol) were added to a jacketed reactor vessel containing toluene (2.2 L) at 20° C., and the resulting mixture was stirred until all solids were dissolved. 2,2,6,6-Tetramethylheptane-3,5-dione (118 g, 0.640 mol), copper(I) chloride (71.8 g, 0.71 mol), and cesium carbonate (749 g, 2.27 mol) were added sequentially, and the jacket temperature was raised to 119° C. The mixture became thick, and stirring resumed as the temperature increased. After 20 hours, the mixture was cooled to 30° C. The organic layer was washed sequentially with water (0.75 L) and with aqueous 15% ammonium hydroxide solution (0.70 L), and then was extracted with aqueous 3M hydrochloric acid solution (1.18 L, 3.55 mol). Ethyl acetate (1.8 L) and aqueous 15% ammonium hydroxide solution (0.500 L, 3.60 mol) were then added sequentially to the acidic aqueous phase. The blue aqueous layer was separated, and the resulting organic layer was washed sequentially with aqueous 15% ammonium hydroxide solution (0.50 L) and with 2:1 water:brine solution (0.30 L). The organic layer and Darco G60 activated charcoal (60 g) were stirred at 45° C. for 1 hour, and then were filtered through a pad of Celite, rinsing with ethyl acetate (0.35 L). The filtrate was concentrated under vacuum and the resulting residue was re-concentrated from methanol (0.30 L) to afford 3-(2-ethoxyphenoxy)pyridine (233 g) as a yellow oil. 1H NMR (400 MHz, DMSO-d6) δ 8.25 (s, 2H), 7.34 (dd, 1H), 7.18 (m, 4H), 6.99 (t, 1H), 4.01 (q, 2H), 1.11 (t, 3H).
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