4-Hydroxybenzoic Acid → Benzoic acid, 4-(phenylmethoxy)-, phenylmethyl ester

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Reaction Steps

4-(Phenylmethoxy)benzoic acid. In a modification of the literature method [E. L. Elied, R. P. Anderson, Reactions of esters with targeting amines. I. Benzyl esters from methyl esters and benzyldimethylamine, J. Am. Chem. Soc., 1952, 74, 547-549] a mixture of 4-hydroxybenzoic acid (27.6 g, 200 mmol), chloromethylbenzene (57.0 g, 450 mmol), potassium carbonate (50 g) and sodium iodide (25 g) was boiled under reflux in acetonitrile (500 mL) for 16 h. The suspension was filtered and the solvent was evaporated from the filtrate under reduced pressure. The residue was recrystallised from ethanol to give phenylmethyl 4-(phenylmethoxy)benzoate (48.8 g, 76%). Phenylmethyl 4-(phenylmethoxy)benzoate (48.8 g, 150 mmol) was boiled under reflux with aqueous sodium hydroxide (2M; 250 mL) and ethanol (250 mL) for 4 h. The ethanol was evaporated under reduced pressure. Water (1000 mL) was added. The white solid was collected by filtration, warmed to 65° C. with aqueous sulphuric acid (2M; 300 mL) for 1 h and extracted with warm ethyl acetate. The ethyl acetate solution was dried with anhydrous magnesium sulphate and the solvent was evaporated under reduced pressure to give 4-(phenylmethoxy)benzoic acid (27.15 g, 80%). The filtrate was washed twice with diethyl ether, acidified by addition of sulphuric acid (2M) and extracted with diethyl ether. Evaporation of the diethyl ether gave a further portion of 4-(phenylmethoxy)benzoic acid (6.0 g, 18%). The total yield was 98%.

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