[NH2:1][C@H:2]([C:5]([OH:7])=[O:6])[CH2:3][OH:4].C([O-])(O)=O.[Na+].[NH:13]([C:28]([O:30][CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)=[O:29])[C@H:14]([C:18](ON1C(=O)CCC1=O)=[O:19])[CH:15]([CH3:17])[CH3:16].Cl.[Na+].[Cl-]>O.O1CCOCC1.CCOC(C)=O.CO>[NH:13]([C:28]([O:30][CH2:31][C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1)=[O:29])[C@H:14]([C:18]([NH:1][C@H:2]([C:5]([OH:7])=[O:6])[CH2:3][OH:4])=[O:19])[CH:15]([CH3:17])[CH3:16]L-Serine (104.19 g, 991 mmol) was dissolved in water (1440 mL) in a 4-L Erlenmeyer flask. Solid NaHCO3 (83.25 g, 991 mmol was added and the mixture was stirred at room temperature to give a clear solution. Cbz-Val-OSu (300.0 g, 861 mmol) was added as a solution in 1,4-dioxane (1500 mL), with additional 1,4-dioxane (220 mL) used to rinse. The resulting cloudy mixture became clear after 1.5 h of stirring at 25° C. After 44 h, the mixture was divided into two equal portions. Methanol (700 mL) and 12 N aqueous HCl (42 mL, 504 mmol) was added to each portion, followed by EtOAc (1000 mL) and a solution of NaCl (100 g) dissolved in water (600 mL). The layers were separated and the organic layer was washed with saturated aqueous NaCl (350 mL). The aqueous layers were extracted in succession with EtOAc (1000 mL). The organic layers resulting from work-up of both portions of the reaction were combined, dried (Na2SO4), filtered, and evaporated to give a white solid (351 g). This material was suspended in CH2Cl2 (1500 mL) and stirred for 2 h. The mixture was filtered and the crystals were washed with CH2Cl2 (1000 mL) to give compound 2b as white crystals (262.3 g, 90% yield). 1H NMR (300 MHz, DMSO-d6): consistent with proposed structure for compound 2b. MS: m/z=339.1 (M+1).
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