1-Hydroxybenzotriazole → Cbz-D-hPro-N(Me)Gly-OEt

HRID 1418833

Reaktionsgleichung

Reaktionsgleichung von HRID 1418833
[N:1]1([C:10]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[O:11])[CH2:9][CH2:8][CH2:7][CH2:6][C@@H:2]1[C:3]([OH:5])=O.Cl.[CH2:21]([O:23][C:24](=[O:28])[CH2:25][NH:26][CH3:27])[CH3:22].ON1C2C=CC=CC=2N=N1.C(N(CC)C(C)C)(C)C.Cl.CN(C)CCCN=C=NCC>ClCCl>[N:1]1([C:10]([O:12][CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[O:11])[CH2:9][CH2:8][CH2:7][CH2:6][C@@H:2]1[C:3]([N:26]([CH3:27])[CH2:25][C:24]([O:23][CH2:21][CH3:22])=[O:28])=[O:5]

Komponenten

7

Edukt 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 171173Ethyl N-methylaminoacetate hydrochlorideHCID 688346(2R)-1-((Benzyloxy)carbonyl)piperidine-2-carboxylic acidHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

Produkt 1

HCID 15481639Cbz-D-hPro-N(Me)Gly-OEtAusbeute 80,1 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

To a stirring solution of Cbz-D-hPro-OH (6.0 g, 22.8 mmol), sarcosine ethyl ester hydrochloride (4.38 g, 28.5 mmol), 1-hydroxybenzotriazole (3.08 g, 22.8 mmol), and N,N-diisopropylethylamine (11.9 mL, 68.4 mmol) in dichloromethane (200 mL) was added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (5.46 g, 28.5 mmol). After stirring for 12 hours, the solvent was removed in vacuo and the residue was dissolved in ethyl acetate (500 mL), washed twice with 1N citric acid (200 mL), twice with saturated aqueous NaHCO3, and twice with a saturated aqueous sodium chloride solution. The organic phase was then dried with MgSO4, filtered, and concentrated in vacuo. The residue was chromatographed over silica gel, eluting with a step gradient of hexanes through 50% ethyl acetate/hexanes. Fractions containing product (based on TLC) were combined and concentrated to give 6.62 g (80%) of a colorless oil.

Aufarbeitung

  1. customthe solvent was removed in vacuo
  2. dissolutionthe residue was dissolved in ethyl acetate (500 mL)
  3. washwashed twice with 1N citric acid (200 mL), twice with saturated aqueous NaHCO3
  4. dry with materialThe organic phase was then dried with MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was chromatographed over silica gel
  8. washeluting with a step gradient of hexanes through 50% ethyl acetate/hexanes
  9. additionFractions containing product (based on TLC)
  10. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-14502c810e894b69843cdd3e6730ba19
Quelldatensatz
uspto-grants-1999_03
Patentnummer
US05885967

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