Methyl 4-aminobenzoate → Methyl 4-{[3-methyl-1-(3-methyl-1-benzofuran-2-yl)butyl]amino}benzoate

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Reaction Steps

To a mixture of 3-methyl-1-(3-methyl-1-benzofuran-2-yl)butan-1-one (200 mg) synthesized above, methyl 4-aminobenzoate (140 mg), triethylamine (1.03 mL) and dichloromethane (5 mL) was added titanium (IV) chloride (122 μL) at 0° C., and the mixture was stirred at room temperature overnight. Saturated aqueous sodium hydrogen carbonate solution was added to quench the reaction, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure to give a dark brown solid. To a mixture of the obtained solid, acetic acid (1 mL), methanol (5 mL) and tetrahydrofuran (5 mL) was added sodium cyanoborohydride (175 mg) by small portions, and the mixture was stirred at room temperature for 1 hr. Saturated aqueous sodium hydrogen carbonate solution was added to quench the reaction, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:4, volume ratio) to give the title object compound (254 mg, 78%) as a pale-yellow solid.

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