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With dmap; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; In dichloromethane; at 0 - 21℃;Inert atmosphere;
To a stirred solution of N-Boc-Tyr(OH)-OBut (5) (2.26 g, 6.70 mmol), N-BocALA (3) (1.55 g, 6.70 mmol, 1.0 equiv) and DMAP (8.1 mg, 0.067 mmol, 0.01 equiv) in dry CH2Cl2 (135 mL, 0.05 M) at 0C was added EDC (1.54 g, 8.04 mmol, 1.2 equiv). The reaction mixture was stirred at 0C for 1 h and was warmed to rt. Stirring was continued overnight. Water was added and the organic layer was separated. The aqueous layer was extracted with EtOAc. The combined organic layers were washed with 1 M HCl, H2O, saturated NaHCO3 and brine, successively. The organic phases were dried (Na2SO4), and evaporated. The crude product was purified by flash column chromatography on silica gel (petroleum ether/EtOAc = 5/1 then 1/1) to give N-Boc-5-ALA-Tyr-OBut ester (6) as white foam (3.17 g, 86%).