Hydrochloric Acid → Methyl 1-benzyl-2-oxoazepane-3-carboxylate

HRID 720026Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 720026
[CH:1]([NH:4][CH:5]([CH3:7])[CH3:6])([CH3:3])[CH3:2].[Li:8]CCCC.[Li+].CC([N-]C(C)C)C.[CH2:21]([N:28]1[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30][C:29]1=[O:35])[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.[C:36](=O)([O:39]C)[O:37][CH3:38].Cl>CCOCC.C1COCC1>[Li+:8].[CH3:2][CH:1]([N-:4][CH:5]([CH3:7])[CH3:6])[CH3:3].[CH3:38][O:37][C:36]([CH:30]1[CH2:31][CH2:32][CH2:33][CH2:34][N:28]([CH2:21][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)[C:29]1=[O:35])=[O:39]

Komponenten

10

Edukt 6

HCID 313Hydrochloric AcidHCID 7912DiisopropylamineHCID 12021Dimethyl CarbonateHCID 14910681-Benzylazepan-2-oneHCID 2724682Lithium diisopropylamideHCID 178418339Butyllithium

Produkt 2

HCID 2724682Lithium diisopropylamideHCID 21902024Methyl 1-benzyl-2-oxoazepane-3-carboxylateAusbeute 77 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 3283Diethyl EtherLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

LDA was prepared as follows: Diisopropyl amine (15.2 mL, 110 mmol) freshly distilled under N2 and over CaH2 was added to 110 mL of anhydrous THF in a dry flask, and the solution was cooled to 0° C. in an ice bath. nBuLi (73.3 mL, 111 mmol) was added dropwise, and the reaction was stirred at 0° C. for 1 hour. The freshly prepared LDA was added dropwise to a −70° C. solution of 1-benzyl-azepan-2-one (10.98 g, 544.0 mmol) dissolved in anhydrous Et2O (70 mL). The reaction was stirred at −70° C. for 1 hour, then dimethyl carbonate (4.55 mL, 544 mmol) was added dropwise. The reaction was allowed to warm to room temperature overnight. The reaction was judged complete by HPLC, and was slowly poured into 5N HCl stirring in an ice bath. The organic layer was extracted. The aqueous layer was washed with CH2Cl2 two times, and the combined organics were dried with Na2SO4 and concentrated in vacuo. Crude material was purified on an automated flash column with 80:20 Hexanes:EtOAc to obtain 10.85 g, (77%) of 1-benzyl-2-oxo-azepane-3-carboxylic acid methyl ester as a pale yellow oil. 1H NMR (CDCl3, 300 MHz) 7.42–7.10 (5H, broad s), 4.61 (1H, d, J=14.7 Hz), 4.50 (1H, d, J=14.7 Hz), 3.74 (3H, s), 3.7–3.64 (1H, m), 3.40–3.13 (2H, m), 2.12–1.98 (1H, m), 1.92–1.73 (2H, m), 1.66–1.42 (2H, m), 1.32–1.16 (1H, m) ppm. 13C NMR (CDCl3, 75 MHz) 171.94, 171.04, 137.28, 128.55, 128.24, 127.43, 52.15 (2), 51.27, 48.31, 27.87, 27.41, 25.91 ppm. LRMS: 261.73.

Aufarbeitung

  1. stirringThe reaction was stirred at −70° C. for 1 hour
  2. temperatureto warm to room temperature overnight
  3. extractionThe organic layer was extracted
  4. washThe aqueous layer was washed with CH2Cl2 two times
  5. dry with materialthe combined organics were dried with Na2SO4
  6. concentrationconcentrated in vacuo
  7. customCrude material was purified on an automated flash column with 80:20 Hexanes

Quellen und Nachweise

ORD-Eintrag
ord-677802025be4429095fdfbe07d38fd47
Quelldatensatz
uspto-grants-2006_11
Patentnummer
US07132551B2

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