Br.[CH:2]1([C:5]2[CH:6]=[CH:7][C:8]([CH:13]([C:21]3[CH:26]=[CH:25][C:24]([Cl:27])=[C:23]([Cl:28])[CH:22]=3)[CH2:14][C@@H:15]3[NH:19][C:18](=[O:20])[CH2:17][CH2:16]3)=[N:9][C:10]=2[O:11]C)[CH2:4][CH2:3]1.O>O1CCOCC1>[CH:2]1([C:5]2[C:10](=[O:11])[NH:9][C:8]([C@H:13]([C:21]3[CH:26]=[CH:25][C:24]([Cl:27])=[C:23]([Cl:28])[CH:22]=3)[CH2:14][C@H:15]3[CH2:16][CH2:17][C:18](=[O:20])[NH:19]3)=[CH:7][CH:6]=2)[CH2:4][CH2:3]148% hydrobromic acid (2 mL) was added to a solution of (5R)-5-[2-(5-cyclopropyl-6-methoxypyridin-2-yl)-2-(3,4-dichlorophenyl)ethyl]pyrrolidin-2-one (120 mg) in 1,4-dioxane (4 mL), and the mixture was stirred at 65° C. for one hour. The reaction solution was poured into water, followed by extraction with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (chloroform:methanol=100:0→90:10) to give an (R,S) mixture of the title compound as a brown amorphous (78 mg). This was preparatively isolated by a chiral HPLC column (CHIRALPAK IB, hexane:ethanol=20:80 v/v, 40° C., 10 mL/min, 210 nm) to give 3-cyclopropyl-6-{(1R)-1-(3,4-dichlorophenyl)-2-[(2R)-5-oxopyrrolidin-2-yl]ethyl}pyridin-2(1H)-one as a colorless amorphous (33 mg) and 3-cyclopropyl-6-{(1S)-1-(3,4-dichlorophenyl)-2-[(2R)-5-oxopyrrolidin-2-yl]ethyl}pyridin-2(1H)-one as a colorless amorphous (21 mg).
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