4-Methylmorpholine → {(1S)-1-[N'-(4-Bromo-benzyl)-hydrazinocarbonyl]-2,2-dimethyl-propyl}-carbamic acid methyl ester

HRID 1158504

Reaktionsgleichung

Reaktionsgleichung von HRID 1158504
[CH3:1][O:2][C:3]([NH:5][C@H:6]([C:11]([OH:13])=O)[C:7]([CH3:10])([CH3:9])[CH3:8])=[O:4].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1.[Br:42][C:43]1[CH:51]=[CH:50][C:46]([CH2:47][NH:48][NH2:49])=[CH:45][CH:44]=1>CCOC(C)=O>[CH3:1][O:2][C:3](=[O:4])[NH:5][C@H:6]([C:11]([NH:49][NH:48][CH2:47][C:46]1[CH:50]=[CH:51][C:43]([Br:42])=[CH:44][CH:45]=1)=[O:13])[C:7]([CH3:10])([CH3:9])[CH3:8]

Komponenten

7

Edukt 5

HCID 79724-MethylmorpholineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 11263950N-(Methoxycarbonyl)-L-tert-leucineHCID 167731114-Bromobenzylhydrazine

Produkt 1

HCID 11710481{(1S)-1-[N'-(4-Bromo-benzyl)-hydrazinocarbonyl]-2,2-dimethyl-propyl}-carbamic acid methyl esterAusbeute 54 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8857Ethyl AcetateLösungsmittel2×

Versuchsvorschrift

N-(Methoxycarbonyl)-(L)-tert-leucine (J. Med. Chem., 41, 3387-3401, 1998) (1.74 g, 9.20 mmol) was dissolved in EtOAc (50 mL) and EDAC (1.94 g, 10.1 mmol), HOBT (1.37 g, 10.1 mmol), and NMM (1.11 mL, 10.1 mmol) were added. The reaction mixture was stirred at room temperature for 30 min and then 4-bromo-benzylhydrazine (prepared as described in Zh. Org. Khim., 28, 43-50, 1992) (2.31 g, 11.5 mmol) in EtOAc (20 mL) was added and the stirring was continued over night. The reaction mixture was washed with saturated NaHCO3 (aq.), H2O and brine and then the organic phase was dried (Na2SO4), filtered and evaporated. The crude product was purified by column chromatography (silica, CHCl3/MeOH, 100:0-96:4) yielding the title compound (1.85 g, 54%) as a white solid.

Aufarbeitung

  1. waitthe stirring was continued over night
  2. washThe reaction mixture was washed with saturated NaHCO3 (aq.), H2O and brine
  3. dry with materialthe organic phase was dried (Na2SO4)
  4. filtrationfiltered
  5. customevaporated
  6. customThe crude product was purified by column chromatography (silica, CHCl3/MeOH, 100:0-96:4)

Quellen und Nachweise

ORD-Eintrag
ord-8a370d24aa9842b380ef3b762ef74a43
Quelldatensatz
uspto-grants-2010_10
Patentnummer
US07807677B2

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