General procedure for the synthesis of N-tert-butoxycarbonyl-N'-benzyloxycarbonyl-L-ornithine from di-tert-butyl dicarbonate and N'-Cbz-D-Ornithine: N'-Cbz-D-Ornithine (22 g, 82.6 mmol) was dissolved or suspended in an aqueous solution (250 mL) of potassium carbonate (12.56 g, 90.9 mmol), followed by addition of 1,4-dioxane (100 mL). A solution of di-tert-butyl dicarbonate (18.93 g, 86.75 mmol) dissolved in 1,4-dioxane (200 mL) was added slowly and dropwise to the reaction mixture over 60 minutes. The reaction mixture was stirred overnight at room temperature and subsequently concentrated under reduced pressure to about 150 mL. water (50 mL) was added and the pH was adjusted to 2-3 with 1 M aqueous hydrochloric acid (about 150 mL). extraction was carried out with ethyl acetate (first 400 mL, then 3 x 300 mL), and the organic phases were combined, and the reaction was carried out in sequence with 10 mM aqueous hydrochloric acid (100 mL), saturated NH4Cl aqueous solution (200 mL) and water (100 mL) to wash. Finally, it was washed with brine (250 mL) and dried over sodium sulfate. After filtration, the solvent was evaporated to give a pale yellow oil, which gradually became foamy and eventually hardened to a solid during vacuum drying (27.8 g, 92% yield). The product was characterized by 1H NMR (300 MHz, DMSO-d6): δ (ppm) 1.38 (s, 9H), 1.4-1.59 (m, 3H), 1.65 (m, 1H), 2.98 (m, 2H), 3.83 (m, 1H), 5.0 (s, 2H), 7.07 (d, 1H, 3J = 8.0 Hz), 7.25 (t. 1H, 3J = 5.5Hz), 7.34 (m, 5H), 12.42 (s, 1H); molecular formula C18H28N2O6 (molecular weight 366.4).
