Lithium Hydroxide → HCID 44227312, compound

Participants

Reaction Steps

Ethyl 3-{[(4-{[cyclohexyl(3-methyl-1-benzofuran-2-yl)methyl]amino}phenyl)carbonyl](methyl)amino}propanoate (9.85 g) synthesized in Example A16 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 (4.85 g, 99.9% ee). To a mixture of the obtained amorphous form, ethanol (20 mL) and tetrahydrofuran (20 mL) was added 1N lithium hydroxide (22 mL), and the mixture was stirred at room temperature for 1 hr and concentrated under reduced pressure. The residue was dissolved in water (20 mL), and 1N hydrochloric acid (20 mL) was added at 0° C. The resulting precipitate was collected by filtration to give the title object compound (4.41 g, 97%, 99.9% ee) as a white solid. The obtained white solid (50 mg) was crystallized from ethanol/water to give ethanol-containing crystals (41 mg). The ethanol-containing crystals (35 mg) were recrystallized from diethyl ether to give colorless crystal (18 mg) free of solvent.

Provenance & Evidence