Reaction Steps
Compound 4 (139 mg, 0.6 mmol) was dissolved in dry CH2Cl2 (6 mL) and treated with L-Phe-OMe.HCl (142 mg, 0.66 mmol), EDCI.HCl (138 mg, 0.72 mmol), DIEA (128 μL, 0.72 mmol). The reaction mixture was stirred for 24 h, diluted with EtOAc, acidified with 10% citric acid and extracted with EtOAc (3×). The combined organic layers were washed with saturated NaHCO3 and brine, dried (MgSO4) and concentrated. The crude residue was purified via column chromatography eluting with EtOAc/hexane to afford pure product 5 (188 mg, 80%) as a white solid. An analytical sample was purified by recrystallization (hexanes/EtOAc): m.p. 119.5-121° C. TLC Rf=0.60 (EtOAc/hexanes, v/v, 1:1). 1H NMR (500 MHz, CDCl3) δ 7.32-7.23 (m, 3H), 7.17-7.15 (m, 2H), 6.36 (bd, J=6.6 Hz, 1H), 4.96-4.89 (m, 1H), 4.54 (bs, 1H), 3.72 (s, 3H), 3.18, 3.07 (AB of ABX, JAB=13.9 Hz, JAX=6.0 Hz, JBX=7.2 Hz, 2H), 3.00-2.84 (m, 2H), 2.08-1.98 (m, 1H), 1.73-1.49 (m, 3H), 1.44 (s, 9H), 1.47-1.36 (m, 1H), 0.85 (t, J=7.5 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 175.23, 172.47, 156.43, 136.40, 129.38, 128.79, 127.28, 79.42, 53.16, 52.46, 46.46, 38.72, 38.18, 33.16, 28.61, 26.21, 12.04; HRMS m/z (ESI): calc. for C21H32N2O5Na [M+Na]+415.2204, found 415.2199. Optical rotation: [α]rtD+14.9 (c 1.06, CHCl3). In addition, N-Boc γ-lactam (7.6 mg, 6%) was isolated via column chromatography eluting with EtOAc/hexane.
