Reaction Steps
Nε -Carbobenzyloxy-L-lysine (30.0 g, 0.107 mmol) was dissolved in a solution of 2N NaOH (60 mL) and dioxane (150 mL) under nitrogen. After about 15 minutes at room temperature, the mixture was cooled to about 0° C. and subsequently treated with additional 2N NaOH (60 mL) and p-toluenesulfonyl chloride (20.4 g, 0.107 mmol) in 5 g portions over about 15 minutes. The mixture was stirred at about 0° C. for about 1 hour and at room temperature for about 18 hours before it was neutralized to pH 6 with 1N HCl. The mixture was then diluted with ethyl acetate and the organic phase was separated and washed with brine. The aqueous phase was extracted twice more with ethyl acetate and the combined organic phases were treated further as mentioned above. Following drying and solvent evaporation of the combined organic phases, the residue was first pre-columned on silica gel (elution with 10% methanol in dichloromethane) and subsequently recrystallized from ethyl acetate/hexanes (2:1) to give 37.67 g (81%) of the title compound as a white solid, m.p. 120°-121° C.; 1H NMR (CDCl3) δ 8.37 (v br s, 0.5H), 7.71 (d, J=8.0 Hz, 2H), 7.32 (s, 5H), 7.23 (d, J=7.6 Hz, 2H), 6.49 and 4.89 (2m, 1H), 5.73 (d, J=8.4 Hz, 1H), 5.10 and 5.04 (2s, 2H), 3.91 (m, 1H), 3.17-3.02 (m, 2H), 2.35 (s, 3H), 1.73-1.66 (m, 2H), 1.40-1.24 (m, 4H); 13C NMR (CDCl3) ppm 199.88, 175.06, 174.57, 158.37, 156.89, 143.66, 136.86, 136.32, 129.66, 128.54, 128.10, 127.19, 67.47, 66.89, 55.28, 40.95, 40.44, 32.25, 29.10, 28.75, 21.77, 21.46; IR (KBr, cm-1) 3382, 3264, 2950, 1738, 1656 1550, 1334, 1286, 1160, 1092, 818, 678, 568; MS m/z (MH+) 435.1590, obsd 435.1595.
