1,2-Dichloroethane → Benzyl-2-{2-[5-(tert-butoxycarbonyl)-4-oxopentanamido]-acetamido}-acetate

HRID 1617000

Reaktionsgleichung

Reaktionsgleichung von HRID 1617000
[C:1]([O:5][C:6]([CH2:8][C:9](NCC(O)=O)=[O:10])=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH2:16](Cl)[CH2:17]Cl.[CH2:20]([O:27][C:28](=[O:35])[CH2:29][NH:30][C:31](=[O:34])[CH2:32][NH2:33])[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1.[C:36](O)(C(F)(F)F)=[O:37].C(N(CC)CC)C>CN(C=O)C>[CH2:20]([O:27][C:28](=[O:35])[CH2:29][NH:30][C:31](=[O:34])[CH2:32][NH:33][C:36](=[O:37])[CH2:16][CH2:17][C:9](=[O:10])[CH2:8][C:6]([O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[O:7])[C:21]1[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=1

Komponenten

7

Edukt 5

HCID 111,2-DichloroethaneHCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 337781Benzyl 2-[(2-aminoacetyl)amino]acetateHCID 866677562-[2-(tert-Butoxycarbonyl)-acetamido]-acetic acid

Produkt 1

HCID 68088980Benzyl-2-{2-[5-(tert-butoxycarbonyl)-4-oxopentanamido]-acetamido}-acetateAusbeute 42,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
-10 °C

Versuchsvorschrift

2-[2-(tert-butoxycarbonyl)-acetamido]-acetic acid (15a, 0.38 g, 1.85 mmol) was dissolved in DMF (15 mL), and the solution was cooled down to −10° C., added with EDC (0.40 g, 2.03 mmol) for stirring 15 min, and then added with benzyl-2-(2-aminoacetamido)acetate, TFA salt (15b, 0.68 g, 1.85 mmol) and triethylamine (0.4 mL, 2.88 mmol). Finally, the reaction was replaced under room temperature with continuous stirring for 6 h. After the reaction was completed, DMF was removed by concentration under reduced pressure. The obtained solid was dissolved in ethyl acetate (50 mL), and then the organic phase was washed by H2O, 5% citric acid, H2O, saturated NaHCO3 and saturated NaCl solution separately, and dried over MgSO4 and concentrated under reduced pressure to remove ethyl acetate to obtain brown solid product. The product was purified by silica gel column chromatography, while the proportion of eluting solution is dichloromethane:methanol=1:0, 24:1, 19:1 in order, and yellow solid product 16 (0.33 g; 42.3%) is obtained. 1H-NMR (200 MHz) (DMSO) δ: 8.33 (t, 1H, Gly4-NH), 8.21 (t, 1H, Gly3-NH), 8.06 (t, 1H, Gly2-NH), 7.33-7.42 (m, 5H, ArH), 7.03 (t, 1H, Gly1-NH), 5.19 (s, 2H, CO2CH2Ph), 3.92 (d, 2H, Gly4-H), 3.76 (d, 4H, Gly3 and Gly2-H), 3.60 (d, 2H, Gly1-H), 1.40 [s, 9H, CO2C(CH3)3].

Aufarbeitung

  1. customwas replaced under room temperature
  2. stirringwith continuous stirring for 6 h
  3. customDMF was removed by concentration under reduced pressure
  4. dissolutionThe obtained solid was dissolved in ethyl acetate (50 mL)
  5. washthe organic phase was washed by H2O, 5% citric acid, H2O, saturated NaHCO3 and saturated NaCl solution separately
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated under reduced pressure
  8. customto remove ethyl acetate
  9. customto obtain brown solid product
  10. customThe product was purified by silica gel column chromatography, while the proportion of eluting solution

Quellen und Nachweise

ORD-Eintrag
ord-b9013a94ff90493ebcc100e9d4ceadfb
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08765934B2

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