Hydrochloric Acid → N-(3,4-dihydroxyphenethyl)-2-hydroxy-2-(4-hydroxy-3 methoxyphenyl)acetamide

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Reaction Steps

2-(4-Hydroxy-3-methoxyphenyl)-2-hydroxyacetic acid (2 g, 10:1 mmol) and N-hydroxysuccinimide (1.16 g, 10.1 mmol) were dissolved in 1,4-dioxane (120 ml) under nitrogen. N,N′-dicyclohexylcarbodiimide (2.08 g, 0.1 mmol) was added to the mixture at room temperature, and the mixture was stirred at this temperature for 48 h. The by-product which precipitated out was filtered off, and the filtrate was evaporated under reduced pressure. The product was chromatographed on silica gel with the eluent ethyl acetate. The yield was 1.72 g (58%). A solution of 2-(3,4-dihydroxyphenyl)-ethylamine hydrochloride (385 mg, 2.03 mmol) in water (30 ml) was added to a solution of the product (500 mg, 1.69 mmol) in 30 ml of 1,4-dioxane under nitrogen, followed by sodium hydrogencarbonate (142 mg, 1.69 mmol). The mixture was stirred at 50° C. for 4 h, then rendered acidic using 10% strength hydrochloric acid, and the reaction solution was extracted 3 times with ethyl acetate (a total of 90 ml). The organic phase was washed with saturated NaCl solution, dried over Na2SO4 and filtered, and the filtrate was evaporated under reduced pressure. Purification was carried out by chromatography on silica gel using the eluent ethyl acetate. The yield was 231 mg of an amorphous, colorless solid (41% of theory).

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