Sodium Carbonate → 4-[4-Fluoro-3-(trifluoromethyl)phenyl]pyridine

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Reaction Steps

First, 4-(4-fluoro-3-trifluoromethyl-phenyl)-pyridine 73 was prepared as follows. To a suspension of pyridine-4-boronic acid (2.59 g, 21.1 mmol) in 1-propanol (60 mL) was added 5-bromo-2-fluorobenzotrifluoride (5.12 g, 21.1 mmol) and triphenylphosphine (0.160 g, 0.610 mmol), followed by sodium carbonate in water (2.0 M, 12 mL). The mixture was purged with nitrogen gas for 10 minutes. To it was added palladium(II) acetate (0.044 g, 0.196 mmol) and it was then heated under reflux for 4 hours. The reaction mixture was partitioned between ethyl acetate (200 mL) and water (200 mL). The organic layer was separated, washed with brine (3×200 mL), dried over MgSO4, then filtered. After evaporating the solvent, the crude material was loaded to a silica gel column, eluting with 60% ethyl acetate in hexane to give a white solid 73 (2.73 g, 54%). 1H-NMR (CDCl3, 400 MHz) δ 7.34-7.42 (m, 1H), 7.61-7.65 (m, 2H), 7.80-7.93 (m, 2H), 8.73-8.84 (m, 2H); MS (DCI) m/z 242, 243 (M+H)+.

Provenance & Evidence