A suspension of (2S,4R)-methyl 4-benzamido-1-(2-(tert-butoxycarbonyl-amino)acetyl)pyrrolidine-2-carboxylate (800 g, 1.97 moles) in MeOH (6.5 L) was heated to 35° C. for dissolution. The solution was cooled to 12° C. A solution of NaOH (prepared from 273 g of 50% aq NaOH and 1.7 kg of water) was added dropwise, while keeping reaction mixture temperature at 10-15° C. The reaction was stirred at 10-15° C. for 1 h and was monitored by HPLC. When the reaction was deemed to be complete (<0.5% of starting material) by HPLC, a solution of 2N HCl (1 L) was added slowly while maintaining the reaction mixture temperature below 20° C. MeOH was removed under vacuum and EtOAc (11.5 L) was charged. More 2N HCl was added to adjust the solution to pH 1-2. The organic phase was separated and washed with water (2×0.8 L). Ethyl acetate was distilled under vacuum until the batch volume reached about 3.5 L. Acetone (6.5 L) was added. Acetone was distilled at atmospheric pressure until the final volume reached about 3.5 L. The mixture was cooled to 45° C. Heptane (3.3 L) was added over 10 min at 45-50° C. The resulting slurry was cooled to room temperature over 30 min, and stirred at room temperature for 1 h. The white solid was filtered and washed with acetone (2×1 L). The wet cake was dried under vacuum to give 650 g of product (85%). The HPLC area purity was >99%. 1H NMR (DMSO-d6, δ, ppm, two conformers): 12.6 (bs, 1H), 8.63 and 8.56 (two doublets, J=6.9 Hz, 1H), 7.86-7.82 (m, 2H), 7.57-7.45 (m, 3H), 6.88-6.80 and 6.49 (two multiplets, 1H), 4.66-4.59 (m, 1H), 4.43-4.38 (m. 1H), 3.87-3.64 (m, 3H), 3.48-3.42 (m, 1H), 2.39-2.11 (m, 2H), 1.38 (s, 9H); MS (m/z, positive ESI) for M+H: 392; for M+Na: 41. MS (m/z, positive ESI) for M+H: 392; for M+Na: 414.
