Cl[CH2:2][C:3](Cl)=[O:4].Cl.[Br:7][C:8]1[CH:13]=[CH:12][C:11]([NH:14][C@@H:15]2[CH2:19][NH:18][C@H:17]([CH2:20][OH:21])[CH2:16]2)=[C:10]([N+:22]([O-:24])=[O:23])[CH:9]=1.[OH-].[Na+]>O1CCCC1.O>[Br:7][C:8]1[CH:13]=[CH:12][C:11]([NH:14][C@@H:15]2[CH2:19][N:18]3[C@H:17]([CH2:20][O:21][CH2:2][C:3]3=[O:4])[CH2:16]2)=[C:10]([N+:22]([O-:24])=[O:23])[CH:9]=1Add chloroacetyl chloride (0.49 mol, 55.7 g) drop wise to a solution of (2S,4S)-[4-(4-bromo-2-nitro-phenylamino)-pyrrolidin-2-yl]-methanol, hydrochloride (0.22 mol, 79 g) in tetrahydrofuran/water (1:1) mixture (1180 mL) at room temperature. Maintain the reaction pH between 10-12 by continuous addition of 4 M sodium hydroxide solution. After complete addition of chloroacetyl chloride, stir the reaction mixture for 4 h at room temperature. Remove tetrahydrofuran under reduced pressure and extract the aqueous layer with dichloromethane. Dry the organic layer over anhydrous sodium sulfate, filter, and concentrate to obtain the title compound (50 g, 62%) as an orange solid. 1H NMR (400 MHz, CDCl3) δ 1.59-1.67 (m, 1H), 2.58-2.64 (m, 1H), 3.40 (t, 1H), 3.71 (dd, 1H), 3.91-4.01 (m, 2H), 4.09 (d, 1H), 4.20 (dd, 1H), 4.29-4.35 (m, 2H), 6.75 (d, 1H), 7.54 (dd, 1H), 8.05 (d, 1H), 8.32 (d, 1H).
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