Water → HCID 58047205, compound

Participants

Reaction Steps

A solution of methyl 2-(methoxymethoxy)-4-[(4-benzyloxyphenyl)ethynyl]benzoate (7.37 g, 18.3 mmol) obtained in Reference Example 277 and 10% palladium carbon (50% water-containing product, 11.0 g) in ethanol (50 mL)-THF (10 mL) was stirred under a hydrogen atmosphere (normal pressure) for 2 hr. After filtration of the reaction mixture, the filtrate was concentrated under reduced pressure. To a solution of the obtained residue in DMF (50 mL) were added potassium carbonate (7.63 g, 55.2 mmol) and bromomethylcyclopropane (3.60 mL, 36.7 mmol) and the mixture was stirred at 60° C. for 1 hr. The reaction mixture was diluted with ethyl acetate, and the mixture was washed three times with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was purified by basic silica gel column chromatography (hexane:ethyl acetate=9:1 to 1:1) to give methyl 4-{2-[4-(cyclopropylmethoxy)phenyl]ethyl}-2-(methoxymethoxy)benzoate (4.69 g, yield 69%). A solution of methyl 4-{2-[4-(cyclopropylmethoxy)phenyl]ethyl}-2-(methoxymethoxy)benzoate (4.69 g, 12.7 mmol) in THF (10 mL) was added to a suspension of lithium aluminum hydride (481 mg, 12.7 mmol) in THF (30 mL), and the mixture was stirred at room temperature for 15 min. To the reaction mixture were successively added water (0.48 mL), 15% aqueous sodium hydroxide solution (0.48 mL) and water (1.5 mL), and the mixture was stirred at room temperature for 30 min. After filtration, the filtrate was concentrated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=7:3 to 0:1) to give the title compound (4.23 g, yield 97%) as an oil.

Provenance & Evidence