Sodium Carbonate → 4-(4-(Trifluoromethyl)phenyl)pyridine 1-oxide

Participants

Reaction Conditions

Reaction Steps

To a mixture of 4-chloropyridine-N-oxide (5.32 g, 41 mmol) and 4-trifluoromethylphenylboronic acid (9.36 g, 49.3 mmol) in anhydrous 1,2-dimethoxyethane (100 ml) was added tetrakis(triphenylphosphine)palladium (0) (1.5 g, 1.3 mmol) and saturated aqueous sodium carbonate solution (50 ml). Nitrogen was bubbled through the mixture for 5 minutes and the reaction was then heated with stirring at 100° C. for 15 hours under an atmosphere of nitrogen. The mixture was allowed to cool to room temperature and the solid was filtered off and washed with 1,2-dimethoxyethane (2×30 ml). The combined organic layers were evaporated under reduced pressure and triturated with diethyl ether (100 ml). The obtained solid was filtered off and dried on the sinter to give 4-(4-trifluoromethylphenyl)pyridine-N-oxide (8.36 g). This compound was suspended in phosphorous oxychloride (50 ml, 536 mmol) and the mixture was heated at 100° C. for 3 hours. After cooling to room temperature the homogeneous dark solution was evaporated under reduced pressure and repartitioned between chloroform and water (200 ml each). The pH was adjusted to 8 by portionwise addition of saturated aqueous sodium carbonate solution and the phases were separated. After two further extractions the combined organic extracts were washed with water and brine and dried over sodium sulfate. After filtration the compound was adsorbed onto silica gel and purified by flash chromatography (10% ethyl acetate-iso-hexane) to yield the title compound (5.5 g, 52%).

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