Reaction Steps
(1R)-2-Acetyloxy-1-methylethyl (2S)-2-amino-3-[3,4-bis(ethoxycarbonyloxy)phenyl]propanoate hydrochloride (14) (10.5 g, 21.7 mmol) was mixed with ethyl acetate (250 mL), and then quickly washed with 5% sodium bicarbonate (100 mL) at 0° C. The organic layer was separated, dried over MgSO4, and then transferred to a flask charged with a mixture of fumaric acid (2.5 g, 21.8 mmol) and ethyl acetate. The mixture was stirred at room temperature for 30 min. The title compound (21) (9.1 g, 83% yield) was crystallized and collected by filtration. M.p.: 78.1-80.7° C. (uncorrected). The melting point as determined using differential scanning calorimeter (DSC) was 82.05° C. (melting enthalpy was 102 μg). 1H NMR (400 MHz, CD3OD): δ 1.20 (d, J=6.4 Hz, 3H), 1.35 (t, J=6.8 Hz, 3H), 1.36 (t, J=6.8 Hz, 3H), 2.03 (s, 3H), 3.17 (dd, J=14.0, 6.8 Hz, 1H), 3.22 (dd, J=14.0, 6.8 Hz, 1H), 4.03 (dd, J=12.0, 6.4 Hz, 1H), 4.22 (dd, J=12.0, 3.2 Hz, 1H), 4.23 (t, J=6.8 Hz, 1H), 4.29 (q, J=7.2 Hz, 2H), 4.30 (q, J=7.2 Hz, 2H), 5.17 (m, 1H), 6.69 (s, 2H), 7.23 (dd, J=8.0, 2.0 Hz, 1H), 7.27 (d, J=2.0 Hz, 1H), 7.30 (d, J=8.0 Hz, 1H). MS (ESI) m/z 442.2 (M+H)+. Calc. For C20H27NO10.2H2O: C, 48.57; H, 5.94; N, 2.36. Found: C, 48.64; H, 5.51; N, 2.38.
