Methylparaben → 4-(2-Chloroethoxy)benzoic acid

Participants

Reaction Conditions

Reaction Steps

Potassium carbonate (7.27 g, 52.6 mmol) and commercially available 1-chloro-2-iodoethane (3.6 mL, 39.5 mmol) were added to a liquid mixture of commercially available methyl p-hydroxybenzoate (2.0 g, 13.1 mmol) and N,N-dimethylformamide (50 mL) under nitrogen atmosphere at room temperature, and the mixture was heated and stirred at 60° C. for 12 hours. The mixture was cooled to mom temperature and then a saturated aqueous ammonium chloride solution, water, and diethyl ether were added to the reaction mixture for partition. The organic layer was washed with water and a saturated saline solution, then dried over anhydrous magnesium sulfate, and then filtered and concentrated under vacuum. Tetrahydrofuran (25 mL), methanol (10 mL), and a 2 M sodium hydroxide solution (10 mL) were added to the residue at morn temperature, and the mixture was heated and stirred at 80° C. for 4 hours. The reaction mixture was cooled to 0° C., acidified with 5 M hydrochloric acid, and then the mixture was diluted with ethyl acetate for partition. The aqueous layer was extracted with ethyl acetate, the combined organic layer was washed with water and a saturated saline solution, then dried over anhydrous magnesium sulfate, and filtered. The solvent was evaporated, the precipitate was separated by filtration with a liquid mixture of ethyl acetate and tetrahydrofuran, the resultant was washed, and the filtrate was concentrated under vacuum. The residue was purified with silica gel column chromatography (n-heptane:ethyl acetate=3:1-2:1-1:1) and the target fraction was concentrated under vacuum to obtain the title compound (278 mg, 11%).

Provenance & Evidence