Ethanol → 3-{[(4-{[Cyclopentyl(3-methyl-1-benzothiophen-2-yl)methyl]amino}phenyl)carbonyl](methyl)amino}propanoic acid

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Reaction Steps

Ethyl 3-{[(4-{[cyclopentyl(3-methyl-1-benzothiophen-2-yl)methyl]amino}phenyl)carbonyl](methyl)amino}propanoate (19.7 g) synthesized in Example A64(1) was fractionated by high performance liquid chromatography (column: CHIRALPAK AD (50 mm ID×500 mL, manufactured by Daicel Chemical Industries, Ltd., mobile phase: hexane/ethanol (500/500), flow rate: 60 mL/min, column temperature: room temperature). The fraction containing an optically active form having a shorter retention time under the above-mentioned high performance liquid chromatography conditions was concentrated to give an amorphous form (8.75 g, 99.9% ee). To a mixture of the obtained amorphous form, ethanol (100 mL) and tetrahydrofuran (100 mL) was added 1N aqueous sodium hydroxide solution (30 mL), and the mixture was stirred at room temperature for 5 hr and concentrated under reduced pressure. The residue was dissolved in water (200 mL), and 1N hydrochloric acid (30 mL) was added at 0° C., 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 the title object compound (7.54 g, 41%, 99.9% ee) as a white solid. The obtained solid was recrystallized from ethanol/water to give colorless crystals.

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