Reaction Steps
The experimental procedure employed for the synthesis of (5S)-6-phenyl-5-[(tert-butyloxycarbonyl)-amino]-4-oxo-hexanoyl-L-proline benzyl ester was followed using the free acid compound 9 (98 mg, 0.3054 mmol, 1.0 eq.), L-phenylalanine methyl ester hydrochloride (55 mg, 0.3054 mmol, 1.0 eq.), 1-Hydroxybenzotriazole hydrate (HOBt) (42 mg, 0.3054 mmol, 1.0 eq.), N-ethyl-N′-(dimethylaminopropyl)-carbodiimide hydrochloride (EDC.HCl) (59 mg, 0.3054 mmol, 1.0 eq.), iPr2NEt (0.11 mL, 0.6110 mmol, 2.0 eq.) and dry DMF/CH2Cl2 (2:8 ratio)(5 mL). Work-up as usual and column chromatography on silica gel elution with 33% EtOAc-hexane afforded the (5S)-6-phenyl-5-[(tert-butyloxycarbonyl)-amino]-4-oxo-hexanoyl-L-phenylalanine methyl ester (NACE 119) as a pale viscous oil (0.140 g, 95%); Rf 0.35 (40% EtOAc-hexane); IR (liquid film) ν 1645 (CO) and 3170 (broad, NH) cm−1; 1H NMR (400 MHz, CDCl3) δH 1.39 (9H, s, (CH3)3), 2.44 (2H, t, J=6.2 Hz, —CH2CO), 2.77 (2H, m, —CH2CO), 2.91 (1H, dd, J=6.6 and 13.2 Hz, —CHαPh), 3.00-3.15 (3H, m, —CHβPh and —CH2Ph), 3.71 (3H, s, OCH3), 4.49 (1H, m, —CH—), 4.84 (1H, m, —CH—), 5.07 (1H, d, J=7.0 Hz, —NH), 6.03 (1H, d, J=7.7 Hz, —NH) and 7.08-7.58 (10H, m, Ar—H); 13C NMR (100 MHz, CDCl3) δC 28.2, 29.3, 29.4, 37.8 (2C), 52.2, 53.2, 60.3, 64.8, 126.9 (2C), 127.0, 127.1, 128.4, 128.5, 128.6, 129.2, 129.3, 129.5, 135.8, 136.4, 158.3, 171.9, 172.0 and 206.7; EI-MS m/z calcd for C27H34N2O6 (M+) 482.2417, found 482 (M+).
