1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide Hydrochloride [Coupling Agent for Peptides Synthesis]

Typical Procedure:
To a solution of Boc-ΔTyr(Cl₂Bzl)-OH (307 mg, 0.7 mmol), glycinamide hydrochloride (77.4 mg, 0.7 mmol) and Et₃N (0.1 mL, 0.7 mmol) in DMF (7 mL) is added EDC·HCl (148 mg. 0.77 mmol) and HOBt (129 mg, 0.84 mmol) at -10°C. The reaction mixture is stirred for 2 h at 0°C. and overnight at room temperature. After the solution is evaporated, the residual is dissolved in EtOAc. The solution is washed with 4% NaHCO₃, 10% citric acid and water. The solution is dried and evaporated. The purification is carried out by silica gel column chromatography to give Boc-ΔTyr(Cl₂Bzl)-Gly-NH₂ (317 mg, 85% yield).
(Δ means dehydro-form.)

Typical Procedure: To a 50 mL round bottom flask equipped with a magnetic stir bar and septum is added 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride 2.54 g (13.3 mmol), 4-dimethylaminopyridine 1.62 g (13.3 mmol), carboxylic acid 1.02 g (2.46 mmol), alcohol 0.96 g (3.98 mmol) and CHCl3 (15 mL), and the reaction mixture is stirred at room temperature for 2.5 days. Acetic acid (0.5 mL) is added and the reaction mixture is stirred for 10 min to convert excess alcohol to a more easily separable acetate. The mixture is washed with saturated aqueous NH4Cl solution, diluted with Et2O, and the layers are dried, filtered and concentrated under reduced pressure. The crude material is chromatographed by silica gel column chromatography (hexane：ethyl acetate = 9：1) to give the desired product 1.25 g (1.96 mmol, 80%).