Reaction Steps
A solution containing 6-[(Naphthalene-2-carbonyl)-amino]-5-oxo-1,2,3,5,6,7,10,10a-octahydro-pyrrolo[1,2-a]azocine-3-carboxylic acid (425 mg, 1.12 mmol), EDCI (240 mg, 1.25 mmol), HOBt (170 mg, 1.25 mmol), and NMM (0.15 mL, 1.25 mmol) in THF (15 mL) is stirred at rt for 20 min. A solution of 3-Amino-4-(tert-butyl-dimethyl-silanyloxy)-butyric acid benzyl ester (400 mg, 1.25 mmol, prepared by methods outlined in Chem. Pharm. Bull. 1999, 47, 11–21) in 5 mL of THF is added and the solution is stirred at rt for 12 h. The solution is poured into water and the aqueous solution is extracted with EtOAc. The combined organic extracts are washed with saturated NaHCO3 and brine, dried (Na2SO4), filtered, concentrated, and purified by flash chromatography on silica gel (hexane/EtOAc) to yield 520 mg of desired product. 1H NMR (CDCl3) δ 8.33 (s, 1H), 7.88 (m, 4H), 7.56 (m, 3H), 7.36 (m, 4H), 7.14 (d, J=8.4 Hz, 1H), 5.86 (m, 1H), 5.75 (m, 1H), 5.46 (m, 1H), 5.13 (s, 2H), 4.63 (d, J=7.5 Hz, 1H), 4.40 (m, 1H), 5.75 (m, 1H), 5.46 (m, 1H), 5.13 (s, 2H), 4.63 (d, J=13.5 Hz, 1H), 2.94 (m, 1H), 2.75–2.56 (m, 2H), 2.37–2.21 (m, 2H), 2.10–1.70 (m, 3H), 0.93 (s, 9H), 0.08 (s, 3H), 0.07 (s, 3H).
