Pyridine → 3-Hydroxy-4-methylbenzonitrile

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Reaction Steps

29.8 g (196 mmol) of 3-hydroxy-4-methylbenzoic acid was dissolved in 450 ml of tetrahydrofuran. 43.1 ml (450 mmol) of ethyl chloroformate and 62.7 ml (450 mmol) of triethylamine were added to the solution at 0° C. After stirring for 20 minutes, triethylamine hydrochloride thus formed was removed by the filtration. The filtrate was added to 300 ml of a solution obtained by bubbling ammonia in tetrahydrofuran at 0° C. After stirring at room temperature for 2 hours, the solvent was evaporated under reduced pressure. The residue was dissolved in 500 ml of dioxane. 38.8 ml (274 mmol) of trifluoromethanesulfonic anhydride and 75 ml (931 mmol) of pyridine were added to the solution at 0° C. After stirring at room temperature for 18 hours, the solvent was evaporated under reduced pressure. The residue was isolated with chloroform as the extractant in the same manner as that of step 1 in Example 1 to obtain an oily residue, which was dissolved in 330 ml of tetrahydrofuran/methanol (1/1). 165 ml (167 mmol) of 1 N aqueous sodium hydroxide solution was added to the solution at room temperature. They were stirred for 4 hours. The solvent was evaporated under reduced pressure. The residue was washed with dichloromethane and then made acidic with 1 N aqueous hydrogen chloride solution. Then the crude product was separated with ethyl acetate as the extractant in the same manner as that of step 1 in Example 1 to obtain the crude product, which was purified by the silica gel column chromatography to obtain the title compound.

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