Sodium Hydroxide → HCID 44227315, compound

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Reaction Steps

Ethyl 3-[{[4-({1-[5-(cyclopropylmethoxy)-3-methyl-1-benzofuran-2-yl]-2-methylpropyl}amino)phenyl]carbonyl}(methyl)amino]propanoate (18.23 g) obtained in Example A75(4) 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 (1:1-1:4, volume ratio) as a mobile phase at room temperature and at a flow rate 60-50 mL/min. The resulting fraction containing an optically active form having a longer retention time was concentrated to give an amorphous form (9.08 g, 99.9% ee). The obtained amorphous form (4.73 g) was dissolved in ethanol (19 mL) and tetrahydrofuran (19 mL), 1N aqueous sodium hydroxide solution (18.7 mL) was added, and the mixture was stirred at room temperature for 20 min. The solvent was evaporated under reduced pressure. Water (40 mL) was added, and the mixture was neutralized with 1N hydrochloric acid (18.7 mL) under ice-cooling and stirred for 30 min. The resulting precipitate was collected by filtration, and dried to give the title compound (4.02 g, 90%, 98.8% ee) as a colorless amorphous form. The obtained colorless amorphous (500 mg) was dissolved in ethyl acetate, and the mixture was washed with water and saturated brine. The organic layer was dried over anhydrous magnesium sulfate. After filtration, the filtrate was concentrated to give a colorless amorphous. The obtained colorless amorphous was crystallized from ethyl acetate/hexane to give colorless crystals (401 mg). In addition, an amorphous product (60 mg) obtained by partitioning was crystallized from diethyl ether/hexane to give colorless crystals (45 mg).

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