Triethylamine → (2-{4-[4-(2-Benzyloxycarbamoylethyl)-phenoxy]-phenyl}-1-dimethylcarbamoyl-ethyl)-carbamic acid tert-butyl ester

HRID 748979Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 748979
[C:1]([O:5][C:6]([NH:8][CH:9]([C:29](=[O:33])[N:30]([CH3:32])[CH3:31])[CH2:10][C:11]1[CH:28]=[CH:27][C:14]([O:15][C:16]2[CH:21]=[CH:20][C:19]([CH2:22][CH2:23][C:24](O)=[O:25])=[CH:18][CH:17]=2)=[CH:13][CH:12]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].ON1C2C=CC=CC=2N=N1.Cl.CN(C)CCCN=C=NCC.C(N(CC)CC)C.Cl.[CH2:64]([O:71][NH2:72])[C:65]1[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=1>CN(C=O)C.CCCCCC.C(OCC)(=O)C>[C:1]([O:5][C:6](=[O:7])[NH:8][CH:9]([C:29](=[O:33])[N:30]([CH3:32])[CH3:31])[CH2:10][C:11]1[CH:28]=[CH:27][C:14]([O:15][C:16]2[CH:21]=[CH:20][C:19]([CH2:22][CH2:23][C:24](=[O:25])[NH:72][O:71][CH2:64][C:65]3[CH:70]=[CH:69][CH:68]=[CH:67][CH:66]=3)=[CH:18][CH:17]=2)=[CH:13][CH:12]=1)([CH3:2])([CH3:3])[CH3:4]

Komponenten

9

Edukt 5

HCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 102312Benzyloxyamine hydrochlorideHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 597628113-{4-[4-(2-Tert-butoxycarbonylamino-2-dimethylcarbamoyl-ethyl)-phenoxy]-phenyl}-propionic acid

Produkt 1

HCID 59762819(2-{4-[4-(2-Benzyloxycarbamoylethyl)-phenoxy]-phenyl}-1-dimethylcarbamoyl-ethyl)-carbamic acid tert-butyl esterAusbeute 79,7 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6228DimethylformamideLösungsmittelHCID 8058HexaneLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
2.5 °C

Versuchsvorschrift

The acid compound 6 (4.8 g, 10.5 mmol) was dissolved in dry DMF and cooled to 0-5° C. 1-Hydroxybenzotriazole (1.56 g, 11.5 mmol), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI, 2.0 g, 10.5 mmol), and triethylamine (4.4 mL, 31.6 mmol) were added to the above mixture followed by stirring for 15 min. O-Benzylhydroxylamine hydrochloride (1.85 g, 11.5 mmol) was added and the mixture was allowed to come to room temperature and stirred for 18 h. The solvent was evaporated under reduced pressure and the residual oil was taken up in EtOAc (100 mL). The organic layer was extracted with 2.0 M HCl (1×20 mL), saturated NaHCO3 (1×20 mL), and brine (1×50 mL). The resulting EtOAc layer was dried and concentrated to yield the crude product. Flash chromatography (30-70% ethyl acetate in hexane containing 1% acetic acid) yielded the desired benzyl hydroxamate 7 (4.7 g, 78%). 1H NMR (400 MHz, DMSO-d6): 10.96 (s, 1H), 7.32-7.38 (m, 5H), 7.23 (d, J=8.8 Hz, 2H), 7.17 (d, J=8.4 Hz, 7.06 (d, J=8.0 Hz, 1H), 6.86 (overlapped d, J=8.4 Hz, 4H), 4.72 (s, 2H), 4.53 (m, 1H), 2.90 (s, 3H), 2.69-2.86 (m, 7H), 2.25 (t, J=7.6 Hz, 2H), 1.30 (s, 9H).

Aufarbeitung

  1. customto come to room temperature
  2. stirringstirred for 18 h
  3. customThe solvent was evaporated under reduced pressure
  4. extractionThe organic layer was extracted with 2.0 M HCl (1×20 mL), saturated NaHCO3 (1×20 mL), and brine (1×50 mL)
  5. dry with materialThe resulting EtOAc layer was dried
  6. concentrationconcentrated
  7. customto yield the crude product

Quellen und Nachweise

ORD-Eintrag
ord-52b708c374f04be0bd1c7b8e94505cfa
Quelldatensatz
uspto-grants-2008_07
Patentnummer
US07399786B2

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