Example 5 Synthesis of L-glutamic acid di-tert-butyl ester hydrochloride (15A): L-glutamic acid (14) (4.4 g, 30 mmol) was suspended in chloroform (120 mL) and concentrated sulfuric acid (3 mL, 56 mmol) was added. The suspension was cooled to -78 °C, followed by the slow addition of liquefied isobutene (70 mL). The reaction mixture was gradually warmed to room temperature with stirring and the reaction was continued for 18 hours. Upon completion of the reaction, the suspended solids were completely dissolved to form a clarified solution. The solution was bubbled with nitrogen gas for 10 min to remove the residual isobutene, followed by washing with saturated aqueous NaHCO3 solution (2 x 100 mL) and distilled water (100 mL) in that order. The organic layer was dried over anhydrous MgSO4 and concentrated under reduced pressure to remove the solvent. The crude product was placed in a desiccator and dried in the presence of NaOH particles for 48 h to give L-glutamic acid di-tert-butyl ester (15) (6.7 g, 86% yield) as an oil.1H-NMR (δH): 1.39 (s, 9H, COO-t-Bu), 1.41 (s, 9H, COO-t-Bu), 1.60-1.90 (m, 2H CH2CH(NH2)-), 2.15-2.35 (m, 2H, CH2COO), 2.85 (s, 2H, NH2), 3.20-3.35 (m, 1H, CH(NH2)-).MS (ESI): m/z 260 ([M+H]+, 100%), 283 ([M+Na]+, 10%).
