C(=O)(O)[O-].[Na+].Cl.[NH2:7][C@@H:8]1[CH2:12][N:11]([C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[C@H:10]([C:20]([O:22][CH3:23])=[O:21])[CH2:9]1.NC1CNC(C(OC)=O)C1.[C:34](Cl)(=[O:41])[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1>CCOC(C)=O.O>[C:34]([NH:7][C@@H:8]1[CH2:12][N:11]([C:13]([O:15][C:16]([CH3:17])([CH3:18])[CH3:19])=[O:14])[C@H:10]([C:20]([O:22][CH3:23])=[O:21])[CH2:9]1)(=[O:41])[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1To a 250-mL three-necked round bottom flask, with mechanical stirring, was charged 4.8 g (56.8 mmol) of sodium bicarbonate followed by 48 mL water. To this stirred solution was charged (2S,4S)-1-tert-butyl 2-methyl 4-aminopyrrolidine-1,2-dicarboxylate hydrochloride A (4 g, 14.2 mmol; prepared from commercially available methyl 4-aminopyrrolidine-2-carboxylate) and EtOAc (40 mL) (two hazy layers observed). The reaction mixture was cooled to 5-10° C. with an ice-bath. Benzoyl chloride (2.0 g, 14.2 mmol) in 8 mL EtOAc was charged dropwise over 10 min maintaining temperature between 5-10° C. The mixture was stirred at 5-10° C. for 1 h and monitored by LC, which showed less than 0.5% by area of benzoyl chloride. The stirring was stopped and the phases were separated. The lower aqueous phase was extracted with EtOAc (2×20 mL). The combined EtOAc layer was washed with 1N HCl (20 mL), saturated NaHCO3 aqueous solution (20 mL), brine (20 mL) and dried with Na2SO4. The EtOAc solution was filtered and the filtrate was evaporated to give 4.87 g of (2S,4S)-1-tert-butyl 2-methyl 4-benzamidopyrrolidine-1,2-dicarboxylate B as a white solid (98.2% yield). NMR conforms to structure. HPLC area percent: 99.3%. 1H NMR (DMSO-d6, δ, ppm): 8.46 (d, J=6.6 Hz, 1H), 7.81 (d, J=8.1 Hz, 2H), 7.56-7.44 (m, 3 H), 4.48-4.41 (m, 1H), 4.27 (t, J=7.8 Hz, 1H), 3.79-3.71 (m, 1H), 3.69 (d, J=11.7, 3 H). 3.34-3.25 (m, 1H), 2.59-2.50 (m, 1H), 2.08-1.99 (m, 1H), 1.38 (d, J=18.9 Hz, 9H). MS (m/z, positive ESI, for M+H): 349.
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