Reaction Steps
N-tert-butoxycarbonyl O-propynyl L-serine (14.55 g, 59.82 mmol) was dissolved in DMF (60 mL) and the solution cooled to 0° C. (icebath). Glycine methyl ester hydrochloride (7.51 g, 59.8 mmol) was suspended in DMF (40 mL) and N,N-diisopropylethylamine (7.73 g, 59.8 mmol) added. The resulting suspension was added to the solution of N-tert-butoxycarbonyl O-propynyl L-serine in one portion. HOBt hydrate (9.16 g, 59.8 mmol) dissolved in DMF (20 mL) was added. Finally, EDC hydrochloride (12.61 g, 65.8 mmol) was added in small portions. The reaction mixture was stirred for 1 h at 0° C. after which the icebath was removed and stirring continued for 25 h at room temperature before the solvent was evaporated. The residue was taken up in EtOAc (400 mL) and the solution washed with 1 M aqueous H2SO4 (3×200 mL), 7.5% (w/w) K2CO3 solution (3×200 mL) and saturated brine (200 mL). The solution was dried with anhydrous MgSO4 and the solvent evaporated affording a yellow/orange oil (17.23 g, 92%); δH (300 MHz; d6-DMSO) 8.31 (1H, t, J 6, NH(Gly)), 6.85 (1H, d, J 8, NH(propSer)), 4.26-4.15 (1H, m, CαH(propSer)), 4.13 (2H, t, J 2, CH2CCH), 3.88 (1H, dd, J 17 and 6, CαHH(Gly)), 3.81 (1H, dd, J 17 and 6, CαHH(Gly)), 3.65 (1H, dd, J 10 and 5, CHH), 3.62 (3H, s, OCH3), 3.52 (1H, dd, J 10 and 8, CHH), 3.41 (1H, t, J 2, CCH), 1.39 (9H, s, (CH3)3); δC (75 MHz; d6-DMSO) 170.2, 170.0, 155.1, 79.9, 78.3, 77.2, 69.2, 59.7, 57.6, 54.0, 51.6, 40.6, 28.1, 20.7, 14.0
