3-Hydroxypyridine → 2-Nitro-5-(pyridin-3-yloxy)-4-trifluoromethyl-benzoic acid methyl ester

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Reaction Steps

To a suspension of 198 mg (4.53 mmol) of sodium hydride (65% in oil, washed with pentane) in 2.5 ml of dry tetrahydrofuran a solution of 356 mg (3.74 mmol) of 3-hydroxypyridine in 5 ml of tetrahydrofuran is dropped and the mixture stirred for 1 hour at room temperature. After cooling to 0° C. 1.0 g (3.74 mmol) of 5-fluoro-2-nitro-4-trifluoromethyl-benzoic acid methyl ester dissolved in 10 ml of tetrahydrofuran is added and stirring continued for 7 hours. The reaction mixture is diluted with water and extracted with ethyl acetate. The organic phase is washed with brine, dried over Na2SO4 and evaporated to give an oil which is fractionated by medium pressure chromatography on silica with ethyl acetate/cyclohexane 1:1. The fractions containing the product are combined and evaporated yielding 977 mg of 2-nitro-5-(pyridin-3-yloxy)-4-trifluoromethyl-benzoic acid methyl ester as white powder, m.p. 98-100° C.

Provenance & Evidence