HRID2370904

反应详情

EQUATION

反应方程式

HRID 2370904 的结构方程式

AUXILIARIES

试剂、催化剂与溶剂

1

CONDITIONS

反应条件

温度
0 °C

PROCEDURE

实验过程

O-allyl L-seryl glycine methyl ester trifluoroacetate 20 (4.42 g, 13.4 mmol) was dissolved in CH2Cl2 (40 mL) and N-tert-butoxycarbonyl O-allyl L-seryl α,α-dimethylglycyl L-valine 16 (5.75 g, 13.4 mmol) added. N,N-diisopropylethyl amine (1.73 g, 13.4 mmol) and HOBt hydrate (2.05 g, 13.4 mmol) were added and the solution cooled to 0° C. EDC hydrochloride (2.82 g, 14.7 mmol) was added in small portions together with 10 mL CH2Cl2. The reaction mixture was stirred for 1 h 30 min at 0° C. after which the icebath was removed and the mixture stirred for an additional 26 hours. The solution was diluted by addition of CH2Cl2 (60 mL) and washed with 2 M aqueous H2SO4 (3×90 mL), 7.5% (w/w) aqueous K2CO3 (3×90 mL) and saturated brine (90 mL). The volume was increased by addition of CH2Cl2, the solution dried with anhydrous MgSO4 and the solvent evaporated affording a slightly orange solid (6.14 g, 73%); δH (300 MHz; d6-DMSO) 8.25 (1H, t, J 6, NH(Gly)), 8.14 (1H, s, NH(Aib)), 7.88 (1H, d, J 8, NH(Ser(All))), 7.14 (1H, d, J 8, NH(Val)), 6.84 (1H, d, J 7, NH (Ser(All)1)), 5.92-5.74 (2H, m, CH═CH2), 5.28-5.11 (4H, m, CH═CH2), 4.50 (1H, m, CαH(Ser(All)2)), 4.17-4.09 (2H, m, CαH(Ser(All)1)/CαH(Val)), 3.95 (4H, m, CH2CH═CH2), 3.85 (2H, d, J 6, CαH2(Gly)), 3.61 (3H, s, OCH3), 3.58-3.46 (4H, m, CH2), 2.06-1.95 (1H, m, CH(CH3)2), 1.38 (9H, s, (CH3)3), 1.35 (3H, s, CH3(Aib)), 1.34 (3H, s, CH3(Aib)), 0.83 (3H, d, J 7, CH3(Val)), 0.78 (3H, d, J 7, CH3(Val)); δC (75 MHz; d6-DMSO) 173.9, 170.7, 169.9, 169.8, 169.7, 155.3, 134.8, 116.4, 116.3, 78.4, 71.0, 69.4, 58.2, 56.2, 54.8, 54.5, 52.5, 51.6, 40.6, 30.0, 28.0, 24.9, 24.7, 19.0, 17.8; m/z 650.3366 ([M+Na]+; C29H49N5O10Na requires 650.3377)

WORKUP

后处理

  1. customwas removed
  2. stirringthe mixture stirred for an additional 26 hours
  3. additionThe solution was diluted by addition of CH2Cl2 (60 mL)
  4. washwashed with 2 M aqueous H2SO4 (3×90 mL), 7.5% (w/w) aqueous K2CO3 (3×90 mL) and saturated brine (90 mL)
  5. temperatureThe volume was increased by addition of CH2Cl2
  6. dry with materialthe solution dried with anhydrous MgSO4
  7. customthe solvent evaporated