Methyl 4-aminobenzoate → methyl 4-[(1-{5-chloro-1-[3-(trifluoromethyl)phenyl]-1H-indol-2-yl}heptyl)amino]benzoate

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Reaction Steps

To a mixture of 1-{5-chloro-1-[3-(trifluoromethyl)phenyl]-1H-indol-2-yl}heptan-1-one (709 mg) synthesized above, methyl 4-aminobenzoate (263 mg), triethylamine (1.94 mL) and methylene chloride (10 mL) was added titanium (IV) chloride (229 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 (10 mL) of the obtained oil in tetrahydrofuran were added acetic acid (498 μL) and sodium cyanoborohydride (219 mg), and the mixture was stirred at room temperature for 1.5 hr. 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. The residue was purified by silica gel column chromatography (15% ethyl acetate/hexane) to give the title object compound (645 mg, 68%) as a brown oil.

Provenance & Evidence