tert-Butyl ((1S)-3-Diazo-2-oxo-1-{[(3S)-2-oxopyrrolidin-3-yl]methyl}propyl)carbamate (7)
A solution of N-(tert-butoxycarbonyl)-3-[(3S)-2-oxopyrrolidin-3-yl]-l-alanine (2.72 g, 10.0 mmol) in THF (100 mL) was placed under an atmosphere of N2 and cooled to −23 °C. The resulting clear colorless solution was successively treated with triethylamine (2.1 mL, 15.0 mmol) followed by isobutylchloroformate (1.6 mL, 12.0 mmol). The reaction mixture gradually became opaque with a fine white precipitate and after 1 h was filtered. The colorless filtrate was transferred to a nonground joint flask, cooled to 0 °C, and slowly treated with a solution of diazomethane (∼35 mL, ∼16.6 mmol) in diethyl ether. Note: The diazomethane was generated employing a Diazald kit according to the procedure described in the Aldrich Technical Bulletin AL-180. The resulting yellow clear solution was gradually warmed to room temperature (RT) over 16 h. At this time, N2 was bubbled through the reaction to remove excess diazomethane followed by in vacuo concentration. The resulting residue was diluted with ethyl acetate (100 mL), washed once with sat. NaHCO3 (50 mL), once with brine (50 mL), dried over MgSO4, filtered, and concentrated to give a crude yellow foam. This material was purified by LC (150 g 230–400 SiO2, 3–4% methanol/chloroform) to afford 2.72 g (92%) of the title compound as a light yellow foam. 1H NMR (DMSO-d6) δ 7.63 (bs, 1H), 7.42 (d, J = 8 Hz, 1H), 6.06 (bs, 1H), 3.96 (m, 1H), 3.13 (m, 2H), 2.21 (m, 1H), 2.01 (m, 1H), 1.86 (m, 1H), 1.63–1.52 (m, 2H), 1.38 (s, 9H); MS (ESI+) for C13H20N4O4m/z 319.0 (M + Na)+.