Boc-D-Lys(Z)-OH

106719-44-2

501-53-1

55878-47-2

General procedure for the synthesis of (R)-6-(((benzyloxy)carbonyl)amino)-2-((tert-butoxycarbonyl)amino)hexanoic acid from N-(tert-butoxycarbonyl)-D-lysine and benzyl chloroformate: to an aqueous solution of 1 M NaOH (37 mL), N-(tert-butoxycarbonyl)-D-lysine (3.00 g, 12.2 mmol) was added at room temperature, then slowly dioxane was added until the suspension was completely dissolved. Subsequently, benzyl chloroformate (2.70 g, 15.9 mmol) was added dropwise over 30 min at 0 °C. The reaction mixture was stirred at room temperature for 16 hours. After completion of the reaction, the dioxane was removed by distillation under reduced pressure. The reaction mixture was acidified to pH 2 with 1 M HCl at 0 °C. The aqueous layer was extracted with EtOAc and the combined organic layers were dried with anhydrous Na2SO4, filtered and concentrated under reduced pressure to afford the target compound 29 (4.4 g, 11.6 mmol, 95% yield) as a white foamy solid, which did not require further purification. 1H-NMR (360 MHz, CDCl3): δ (ppm) 7.37-7.23 (m, 5H), 6.18 (br s, 1H), 5.17-4.86 (m, 3H), 4.83 (s, 1H), 4.22-4.04 (m, 1H), 3.13-3.11 (m, 2H), 1.76-1.37 (m, 15H ). 13C-NMR (150 MHz, CDCl3): δ (ppm) 176.4 (CO), 156.8 (CO), 156.0 (CO), 136.6 (Cq), 128.7 (2 × CH), 128.3 (2 × CH), 128.1 (CH), 80.4 (Cq), 66.9 (CH2), 53.3 (CH). 40.7 (CH2), 32.0 (CH2), 29.3 (CH2), 29.5 (3×CH3), 22.1 (CH2). MS (ESI) m/z (%): (C14H20N2O4) 222 (14), (C7H12NO4) 174 (12), 128 (32), 108 (27), 92 (11), (C7H7) 91 (100), 84 (20), 57 (52), 41 (20). MS (ESI) m/z calculated value C14H20N2O4 [M+H-C5H9O2]+, 280.14; measured value, 280.14. LC-MS (ESI) m/z calculated value C19H28N2O6Na [M+Na]+, 403.2; measured value, 403.7. HPLC purity, 96%, tR = 19.7min, Gradient A.