To a mixture of 2-ethyl-1-(3-methyl-1-benzothiophen-2-yl)butan-1-one (1.65 g) synthesized above, methyl 4-aminobenzoate (1.15 g), triethylamine (7.47 mL) and methylene chloride (15 mL) was added a 1.0M solution (8.04 mL) of titanium (IV) chloride in methylene chloride, and the mixture was stirred under argon atmosphere overnight at room temperature. Saturated aqueous sodium hydrogen carbonate solution was added to quench the reaction, methylene chloride was evaporated in an evaporator, and the residue 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 oil. To a mixture of the obtained oil, methyl 4-aminobenzoate (506 mg), triethylamine (7.47 mL) and methylene chloride (30 mL) was added titanium (IV) chloride (882 μL), and the mixture was stirred under argon atmosphere overnight at room temperature. Saturated aqueous sodium hydrogen carbonate solution was added to quench the reaction, and the reaction 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 oil. To a solution (30 mL) of the obtained oil in tetrahydrofuran were added acetic acid (797 μL) and sodium cyanoborohydride (842 mg) and the mixture was stirred at room temperature stirred for 1.5 hr. Saturated aqueous sodium hydrogen carbonate solution was added to quench the reaction, the organic solvent was evaporated in an evaporator, and the residue 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 (10-40% ethyl acetate/hexane) to give the title object compound (580 mg, 23%) as a pale-brown solid.
