反应详情

温度

0 °C

N-tert-butoxycarbonyl O-benzyl L-seryl L-valine 17 (2.20 g, 4.46 mmol) and glycyl glycine methyl ester trifluoroacetate 21 (1.16 g, 4.44 mmol) were dissolved in CH2Cl2 (15 mL). N,N-diisopropylethyl amine (0.57 g, 4.4 mmol) and HOBt hydrate (0.68 g, 4.4 mmol) were added and the solution cooled to 0° C. EDC hydrochloride (0.94 g, 4.9 mmol) was added slowly together with 5 mL CH2Cl2. The reaction mixture was stirred for 1 h 30 min at 0° C. after which the icebath was removed. The mixture was stirred for an additional 23 hours before the volume was increased by addition of CH2Cl2 (20 mL). The solution was washed with 2 M aqueous H2SO4 (3×30 mL), 7.5% (w/w) aqueous K2CO3 (3×30 mL) and saturated brine (30 mL). The volume of the solution was increased, the solution dried with anhydrous MgSO4 and the solvent evaporated affording an off-white solid (2.14 g, 78%); δH (300 MHz; d6-DMSO) 8.25-8.20 (2H, m, NH(Gly1)/NH(Gly2)), 7.93 (1H, d, J 8, NH(Valx)), 7.70 (1H, d, J 9, NH(Valy)), 7.35-7.25 (5H, m, Ph), 7.06 (1H, d, J 8, NH(Ser(Bn))), 4.47 (2H, s, CH2Ph), 4.32-4.23 (2H, m, CαH(Ser(Bn))/CαH(Val)), 4.11 (1H, dd, J, CαH(Val)), 3.86 (2H, m, CαH2(Gly)), 3.75 (2H, d, J 6, CαHH(Gly)), 3.62 (3H, s, OCH3), 3.60-3.53 (2H, m, CH2), 2.01-1.88 (2H, m, CH(CH3)2), 1.38 (9H, s, (CH3)3), 0.85-0.78 (12H, m, CH3); δC (75 MHz; d6-DMSO) 171.1, 170.9, 170.1, 169.6, 169.1, 155.2, 138.1, 128.0, 127.4, 127.3, 78.2, 71.9, 69.8, 58.1, 57.2, 54.5, 51.6, 41.6, 40.5, 30.8, 30.1, 28.1, 19.1, 18.2, 17.8; m/z (ESI) 644.3268 ([M+Na]+; C30H47N5O9Na requires 644.3271)

1. customwas removed
2. stirringThe mixture was stirred for an additional 23 hours before the volume
3. temperaturewas increased by addition of CH2Cl2 (20 mL)
4. washThe solution was washed with 2 M aqueous H2SO4 (3×30 mL), 7.5% (w/w) aqueous K2CO3 (3×30 mL) and saturated brine (30 mL)
5. temperatureThe volume of the solution was increased
6. dry with materialthe solution dried with anhydrous MgSO4
7. customthe solvent evaporated