Methanol → Methyl 3-chloro-4-hydroxyphenylacetate

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Reaction Steps

Sulfuric acid (1 ml) was added dropwise to a solution of 3-chloro-4-hydroxyphenylacetic acid (3.7 g, 20 mmol) in methanol at 0° C. The temperature of the reaction mixture was returned to room temperature and the mixture was stirred for 4 hours. After the solvent was removed under reduced pressure, the residue was poured into water and extracted with ethyl acetate. The organic layer was successively washed with water, a saturated aqueous sodium hydrogencarbonate solution and a saturated aqueous NaCl solution and dried with anhydrous sodium sulfate. The residue obtained by removing the solvent under reduced pressure was subjected to silica gel column chromatography (eluting solvent: ethyl acetate) to obtain give crude methyl (3-chloro-4-hydroxyphenyl)acetate. Pyridine (8 ml, 99 mmol) and trifluoromethanesulfonic anhydride (3.4 ml, 20 mmol) were added dropwise to a solution of the crude compound obtained in the above in methylene chloride (30 ml) under ice-cooling, and the mixture was stirred for 1 hour. The reaction mixture was poured into a 1N aqueous sodium hydroxide solution and extracted with methylene chloride. The organic layer was successively washed with water, diluted hydrochloric acid and a saturated aqueous NaCl solution and dried with anhydrous sodium sulfate. The residue obtained by removing the solvent under reduced pressure was purified by silica gel column chromatography (eluting solvent: n-hexane/ethyl acetate=3/1) to give methyl (3-chloro-4-{[(trifluoromethyl)sulfonyl]oxy}phenyl)acetate as a colorless solid (6.3 g, yield: 95%).

Provenance & Evidence