7-acetyl-6-hydroxy-1-benzofuran-3-one

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of 7-acetyl-6-hydroxybenzofuran-3(2H)-one (0.60 g, 3.1 mmol) in methylene chloride (25 mL) was added with acetic acid (0.25 mL) and N-Boc-piperazine (0.64 g, 3.4 mmol), and the mixture was stirred at room temperature for 10 minutes. The reaction mixture was cooled to 0° C., and then added portionwise with sodium triacetoxyborohydride (0.84 g, 4.1 mmol). After completion of the addition, the ice bath was removed to allow the reaction mixture to warm to room temperature, and the mixture was stirred at the same temperature for 20 hours. The reaction mixture was extracted with methylene chloride, and then the organic layer was successively washed with water, saturated aqueous sodium hydrogencarbonate, and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the residue was subjected to silica gel column chromatography (eluted with chloroform/methanol (100:0→97:3)) to obtain tert-butyl 4-[1-(6-hydroxy-3-oxo-2,3-dihydrobenzofuran-7-yl)ethyl]piperazine-1-carboxylate (0.74 g, 90%). The reaction mixture was cooled to 0° C. After completion of the addition the ice bath was removed to warm to room temperature the mixture was stirred at the same temperature for 20 hours The reaction mixture was extracted with methylene chloride the organic layer was successively washed with water, saturated aqueous sodium hydrogencarbonate, and saturated brine dried over anhydrous magnesium sulfate The solvent was evaporated under reduced pressure the residue was subjected to silica gel column chromatography (eluted with chloroform/methanol (100:0→97:3))

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The synthesis was performed with reference to the known literature (Journal of the Pharmaceutical Society of Japan (Yakugaku Zasshi), Vol. 88, p. 589, 1968). A suspension of aluminum chloride (3.5 g, 26 mmol) in nitrobenzene (10 mL) was stirred at 0° C. under an argon atmosphere. This suspension was added with chloroacetyl chloride (1.1 g, 9.9 mmol), and then the mixture was added dropwise with a suspension of 2,6-dihydroxyacetophenone (1.0 g, 6.6 mmol) in nitrobenzene (6.0 mL). After completion of the addition, the reaction mixture was stirred at 50° C. for 17 hours. The reaction mixture was added with ethyl acetate and ice water, the mixture was stirred at room temperature for 1 hour, and then the organic layer was separated. The organic layer was extracted with 1 N aqueous sodium hydroxide, and the aqueous layer was made acidic with 3 N hydrochloric acid to precipitate solid. The precipitated solid was collected by filtration and dried to obtain 7-acetyl-6-hydroxybenzofuran-3(2H)-one (0.90 g, 71%). After completion of the addition the reaction mixture was stirred at 50° C. for 17 hours the mixture was stirred at room temperature for 1 hour the organic layer was separated The organic layer was extracted with 1 N aqueous sodium hydroxide to precipitate solid The precipitated solid was collected by filtration dried