Water → HCID 11230046, Verbindung

HRID 851934Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 851934
[CH3:1][O:2][C:3]1[CH:21]=[CH:20][C:6]([CH2:7][N:8]2[C:14](=[O:15])[CH2:13][CH2:12][CH2:11][C:10]3[CH:16]=[CH:17][CH:18]=[CH:19][C:9]2=3)=[CH:5][CH:4]=1.[Li+].[CH3:23][CH:24]([N-:26]C(C)C)C.Br[CH2:31][C:32]([O:34][C:35]([CH3:38])([CH3:37])[CH3:36])=[O:33].[OH2:39]>C1COCC1>[OH:39][NH:26][C:24](=[O:33])[CH2:23][CH:13]1[C:14](=[O:15])[NH:8][C:9]2[CH:19]=[CH:18][CH:17]=[CH:16][C:10]=2[CH2:11][CH2:12]1.[C:35]([O:34][C:32](=[O:33])[CH2:31][CH:13]1[C:14](=[O:15])[N:8]([CH2:7][C:6]2[CH:5]=[CH:4][C:3]([O:2][CH3:1])=[CH:21][CH:20]=2)[C:9]2[CH:19]=[CH:18][CH:17]=[CH:16][C:10]=2[CH2:11][CH2:12]1)([CH3:38])([CH3:37])[CH3:36]

Komponenten

7

Edukt 4

HCID 962WaterHCID 79177tert-Butyl bromoacetateHCID 14749841,3,4,5-Tetrahydro-1-[(4-methoxyphenyl)methyl]-2H-1-benzazepin-2-oneHCID 2724682Lithium diisopropylamide

Produkt 2

HCID 11230046HCID 11230046, VerbindungHCID 69004791HCID 69004791, Verbindung

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

A solution of 1-(4-methoxy-benzyl)-1,3,4,5-tetrahydro-benzo[b]azepin-2-one (0.71 mmol) in 2 mL of anhydrous THF is cooled down to −78° C. and freshly prepared LDA (0.85 mmol) is slowly added to the mixture. After the addition, the mixture is allowed to warm up to 0° C., then stirred for 30 minutes and cooled down again to −78° C. Tert-butyl bromoacetate (1.0 mmol) is added. The mixture is stirred at −78° C. for 1 hour and then allowed to warm up to 0° C. To quench the reaction, 1 mL of a mixture of EtOH and water (1:1) is added to the mixture at 0° C. and the mixture is allowed to warm up to room temperature. Water (20 mL) is added followed by extraction (EtOAc, 3×15 mL). The combined organic layers are washed with brine and dried over MgSO4. Solvent is removed under vacuum and the residue is purified by flash column chromatography (silica gel, 0˜25% EtOAc/hexane) to provide the desired product [1-(4-methoxy-benzyl)-2-oxo-2,3,4,5-tetrahydro-1H-benzo[b]azepin-3-yl]-acetic acid tert-butyl ester as white solid. Yield: 30%. 1H NMR (400 MHz, CDCl3): δ 7.24 (m, 2H), 7.13 (m, 4H), 6.75 (d, 2H), 5.10 (d, 1H), 4.80 (d, 1H), 2.86(m, 2H), 2.38˜2.50(m, 2H), 2.17(q, 1H), 1.80˜2.05(m, 2H), 1.40(s, 9H). MS: (ES+): 396 [M+1].

Aufarbeitung

  1. additionAfter the addition
  2. temperaturecooled down again to −78° C
  3. stirringThe mixture is stirred at −78° C. for 1 hour
  4. temperatureto warm up to 0° C
  5. customTo quench
  6. customthe reaction, 1 mL of a mixture of EtOH and water (1:1)
  7. additionis added to the mixture at 0° C.
  8. temperatureto warm up to room temperature
  9. extractionfollowed by extraction (EtOAc, 3×15 mL)
  10. washThe combined organic layers are washed with brine
  11. dry with materialdried over MgSO4
  12. customSolvent is removed under vacuum
  13. customthe residue is purified by flash column chromatography (silica gel, 0˜25% EtOAc/hexane)

Quellen und Nachweise

ORD-Eintrag
ord-635d035f3d2d4eda98cdda68d77e9bd1
Quelldatensatz
uspto-grants-2007_08
Patentnummer
US07253164B2

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