Sodium borohydride → 1-(5-Bromo-3-methyl-1-benzofuran-2-yl)-2-methylpropan-1-ol

Participants

Reaction Steps

1-(5-Bromo-3-methyl-1-benzofuran-2-yl)-2-methylpropan-1-one (6.2 g) synthesized in the above-mentioned (1) was dissolved in tetrahydrofuran (100 mL) and methanol (10 mL), and sodium borohydride (90%, 1.8 g) was added to the solution under ice-cooling. The ice bath was removed, and the reaction mixture was stirred at room temperature for 1 hr then ice-cooled again, and water (10 mL) and 1N hydrochloric acid (50 mL) were carefully added to the mixture, 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 1-(5-bromo-3-methyl-1-benzofuran-2-yl)-2-methylpropan-1-ol (6.1 g, quantitative) as a pale-yellow oil. The obtained oil was dissolved in tetrahydrofuran (50 mL), and thionyl chloride (2.3 mL) was added to the solution at room temperature. The reaction mixture was stirred at room temperature for 30 min then ice-cooled, and saturated aqueous sodium hydrogen carbonate solution (30 mL) was carefully added to the mixture. The reaction mixture was stirred for 10 min, 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 dissolved in dimethylacetamide (100 mL), sodium iodide (3.9 g), sodium carbonate (2.7 g) and ethyl 3-{[(4-aminophenyl)carbonyl](methyl)amino}propanoate (4.4 g) synthesized in Example 2(2) were added to the solution, and the mixture was stirred at 70° C. for 4 hr. After allowing to cool, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate:hexane=1:1, volume ratio) to give the title object compound (1.12 g, 12%) as a yellow oil.

Provenance & Evidence