Sodium Hydroxide → HCID 66778406, compound

Participants

Reaction Steps

Ethyl 3-{[(4-{[2-ethyl-1-(5-fluoro-3-methyl-1-benzofuran-2-yl)butyl]amino}phenyl)carbonyl](methyl)amino}propanoate (9.18 g) obtained in Example A71(5) was dissolved in hexane-ethanol (1:1, volume ratio), subjected to HPLC using CHIRALPAK AD (50 mm ID×500 mL, manufactured by Daicel Chemical Industries, Ltd.), and eluted with hexane-ethanol (1:1, volume ratio) as a mobile phase at room temperature and at a flow rate 60 mL/min. The resulting fraction containing an optically active form having a shorter retention time was concentrated to give an amorphous form (4.56 g, 99.9% ee). The obtained amorphous form (4.56 g) was dissolved in ethanol (19 mL) and tetrahydrofuran (19 mL), 1N aqueous sodium hydroxide solution (18.6 mL) was added, and the mixture was stirred at room temperature for 20 min. The solvent was evaporated under reduced pressure. Water (30 mL) was added, and the mixture was neutralized with 1N hydrochloric acid (18.6 mL) under ice-cooling and stirred for 20 min. The resulting precipitate was collected by filtration, and dried to give the title compound (3.63 g, 86%, 99.9% ee) as a colorless amorphous form. The obtained colorless amorphous (1.0 g) was crystallized from 2-propanol/water to give colorless crystals (927 mg).

Provenance & Evidence