Water → HCID 117701767, compound

Participants

Reaction Steps

To a solution of 8-bromo-7-hydroxy-3-methyl-2-(1-propanoylpiperidin-4-yl)-4H-chromen-4-one (3.82 mol) obtained in Example 32 in dichloromethane (25 mL), diisopropylethylamine (1.32 mL, 7.66 mmol) and chloro(methoxy)methane (345 μL, 4.59 mmol) were added under cooling with ice, and the mixture was stirred for 1 hour under cooling with ice and then at room temperature for 2 hours. Water was added to the reaction solution, followed by extraction with dichloromethane. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (dichloromethane/methanol=98/2) to obtain 847 mg of 8-bromo-7-(methoxymethoxy)-3-methyl-2-(1-propanoylpiperidin-4-yl)-4H-chromen-4-one (yield: 51%). Subsequently, 2-cyclopropyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (181 μL, 0.953 mmol), potassium carbonate (167 mg, 1.21 mmol), and a palladium chloride-dppf complex (40.7 mg) were added to a mixed solution of the obtained compound (104 mg, 0.24 mmol) in N,N-dimethylformamide (2 mL) and water (0.2 mL), and the mixture was stirred at 90° C. for 14 hours under the nitrogen atmosphere. Water was added to the reaction solution, followed by extraction with ethyl acetate. The organic layer was washed with water and saturated brine and dried over anhydrous sodium sulfate, and then the solvent was distilled off under reduced pressure. The obtained residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=50/50→0/100) and then further purified by HPLC to obtain 38 mg of the title compound (yield: 40%) as an oil.

Provenance & Evidence