1,2-Dichloroethane → N-[2(S)-(t-Butoxycarbonylamino)-3(S)-methylpentyl]-N-(1-naphthylmethyl)glycine methionine methyl ester

Participants

Reaction Steps

N-[2(S)-(t-Butoxycarbonylamino)-3(S)-methylpentyl]-N-(1-naphthylmethyl)glycine (8, 2.29 g, 5.53 mmol), dissolved in DMF (20 mL), was treated with HOBT (0.822 g, 6.08 mmol), EDC (1.17 g, 6.08 mmol), and methionine methyl ester hydrochloride (1.21 g, 6.08 mmol). The pH was adjusted to 7.5 with Et3N (1.7 mL, 12 mmol) and the mixture was stirred at ambient temperature for 24 h. The mixture was concentrated, and the residue was partitioned between EtOAc (50 mL) and saturated NaHCO3 solution (25 mL). The aqueous layer was extracted with EtOAc (1×30 mL). The organic layers were combined, washed with brine (1×25 mL), dried (Na2SO4), filtered, and concentrated to give 3.2 g of crude product which was purified by chromatography (silica gel eluting with 1:3 to 1:2 ethyl acetate in hexane) to give pure product. 1H NMR (CD3OD) δ 8.33 (1H, d, J=6 Hz), 7.90 (1H, d, J=6 Hz), 7.82 (1H, d, J=6 Hz), 7.61-7.39 (4H, m), 6.60-6.52 (1H, m), 4.32-4.06 (2H, m), 3.90-3.69 (1H, m), 3.65 (3H, s), 3.27-3.14 (2H, m), 2.93-2.70 (2H, m), 2.19-1.78 (6H, m), 1.63-1.30 (13H, m), 1.19-1.05 (1H, m), 0.95-0.81 (6H, m) ppm.

Provenance & Evidence