Reaction Steps
To a solution of (R)-2-(2-ethoxy-5-oxo-2,5-dihydrofuran-3-ylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (X, R1=Et) (0.14 g, 0.41 mmol) (1H-NMR shows ˜8:2 syn:anti epimers) and lutidine (0.48 mL, 4.1 mmol) in dichloromethane (5 mL) at room temperature under nitrogen was dropwise added trimethylsilyltrifluoromethane-sulfonate (0.48 mL, 2.46 mmol). The reaction was stirred for 0.5 h, then was treated with saturated sodium bicarbonate, was extracted with three portions of dichloromethane, was dried (sodium sulfate), and was evaporated. To the crude intermediate was added 2-benzyloxycarbonylamino-3,3-dimethylbutyric acid (0.12 g, 0.45 mmol) in dichloromethane (5 mL), EDC (0.10 g, 0.51 mmol) and HOBT (0.07 g, 0.51 mmol). The resulting mixture was stirred at room temperature under nitrogen for 3 days. The reaction was diluted with ethyl acetate, was washed with 10% potassium bisulfate, saturated sodium bicarbonate and brine, was dried (sodium sulfate) and was evaporated. Purification by flash chromatography (SiO2) eluted with 1:1 ethyl acetate hexanes provided {1-[2-(2-ethoxy-5-oxo-tetrahydrofuran-3-yl carbamoyl)-pyrrolidine-1-carbonyl]-2,2-dimethylpropyl}carbamic acid benzyl ester (0.12 g, 59% yield) as a white foam. 1H-NMR (500 MHz, CDCl3) δ 7.43 (br d, J=7.7 Hz, 1H), 7.28 (s, 5H), 5.40 (m, 2H), 5.02 (AB q, J=12.1, 31.0 Hz, 2H), 4.55 (m, 2H), 4.29 (d, J=9.6 Hz, 1H), 4.23 (m, 0.2H), 3.85 (m, 0.8H), 3.73 (m, 1H), 3.58 (m, 2H), 2.90 (m, 0.2H), 2.74 (dd, J=17.0, 8.4 Hz, 0.8H), 2.30 (m, 2H), 2.05 (m, 1H), 1.90 (m, 1H), 1.80 (m, 1H), 1.20 (t, J=7.0 Hz, 2.4H), 1.15 (t, J=7.0 Hz, 0.6H), 0.93 (s, 9H) ppm.
