Reaction Steps
2-N-Fluorenylmethoxycarbonylaminohex-4-enoic acid 100 was prepared according to the procedure described by Paquet.230 Fmoc-OSu (2.36 g, 7.00 mmol) was added to a stirred suspension of L-crotylglycine.HCl 101 (1.16 g, 7.03 mmol) and NaHCO3 (2.95 g, 35.0 mmol) in a mixture of acetone:water (1:1, 30 mL). The resultant suspension was stirred at room temperature for 15 h. The reaction mixture was then acidified with concentrated HCl (pH 2) and the acetone was removed under reduced pressure. The resultant suspension was extracted into DCM (3×25 mL) and the combined organic extract was washed with dilute HCl solution (1 M, 2×25 mL), water (2×25 mL), dried (MgSO4) and evaporated under reduced pressure to afford the titled Fmoc-amino acid 100 as colourless solid (1.91 g, 78%), m.p. 119-121° C. νmax (KBr): 3390bm, 3033m, 2961s, 2357w, 1730s, 1651w, 1505w, 1450w, 1395w, 850w cm−1. 1H n.m.r. (300 MHz, CDCl3): δ 1.67 (d, J=6.2 Hz, 3H, H6), 2.37-2.69 (m, 2H, H3), 4.23 (t, J=6.8 Hz, 1H, H9′), 4.42-4.48 (m, 3H, CH2O, H2), 5.30-5.37 (m, 2H, H5, NH), 5.61 (m, 1H, H4), 7.31 (td, J=7.2, 1.3 Hz, 2H, H2′, 7′), 7.34 (td, J=7.4, 1.5 Hz, 2H, H3′, 6′), 7.60 (d, J=7.3 Hz, 2H, H1′, 8′), 7.74 (d, J=7.0 Hz, 2H, H4′, 5′), one exchangeable proton (OH) not observed. 13C n.m.r. (75 MHz, CDCl3): δ 16.7 (C6), 34.1 (C3), 46.2 (C9′), 52.3 (C2), 66.2 (CH2O), 118.9 (C5), 123.0 (C2′, 7′), 124.6 (C3′, 6′), 125.2 (C1′, 8′), 127.5 (C4′, 5′), 129.7 (C4), 140.3 (C8′a, 9′ a), 142.7 (C4′a, 4′ b), 154.9 (OCONH), 175.0 (C1). Mass Spectrum (ESI+, MeOH): m/z 352.1 (M+H)+, C21H22NO4 requires 352.2. Spectroscopic data were in agreement with those reported in the literature.146
