Reaction Steps
Preparation of (3S,6S,10aS)-6-benzoylamino-5-oxo-1,2,3,5,6,7,10,10a-octahydro-pyrrolo[1,2-a]azocine-3-carboxylic acid (2-hydroxy-5-oxo-tetrahydro-furan-3-yl)-amide (11) To a solution of (2-ethoxy-5-oxo-tetrahydro-furan-3-yl)-carbamic acid allyl ester (183 mg, 0.8 mmol) (prepared according to Chapman, K. T. Bioorganic Med. Chem. Lett., 2(6), 1992, pp. 613–618) in dichloromethane (6 mL) is added barbituric acid (300 mg, 1.9 mmol) and tetrakistriphenyl phosphine palladium (92 mg, 0.08 mmol). The solution is stirred for 10 minutes and 6-benzoylamino-5-oxo-1,2,3,5,6,7,10,10a-octahydro-pyrrolo[1,2-a]azocine-3-carboxylic acid, 10, (105 mg, 0.32 mmol) is added followed by 1-hydroxybenzotriazole (99 mg, ) 0.74 mmol) and 1-(3-dimethyl-aminopropyl)-3-ethyl-carbodiimide hydrochloride (141 mg, 0.74 mmol). The solution is stirred for 6 hours. Water is added and the organics are washed with NaHSO4, brine, NaHCO3, and water. The organic layers are dried with MgSO4 and concentrated under reduced pressure. The residue is purified over silica to afford the desired product. 1H NMR (CDCl3): δ 7.83 (d, J=7.3, 2H), 7.54–7.41 (m, 4H), 5.89–5.71 (m, 2H), 5.49 (dt, J=13.9, 7.0 Hz, 1H), 4.61 (m, 2H), 4.33 (m, 1H), 2.99 (m, 3H), 2.41 (m, 3H), 2.18 (m, 2H), 2.06–1.91 (m, 2H). 13C NMR (CDCl3): δ 176.2, 172.9, 171.6, 167.5, 133.4, 132.3, 131.0, 128.8, 127.6, 125.9, 61.7, 59.0, 50.7, 33.9, 33.4, 32.2, 27.0, 20.9. ESI MS 428.01 (M+H).
