Dimethylformamide → Ethyl 1-benzyl-3-methyl-4-oxopiperidine-3-carboxylate

HRID 80848

Reaktionsgleichung

Reaktionsgleichung von HRID 80848
Cl.[CH2:2]([N:9]1[CH2:14][CH2:13][C:12](=[O:15])[CH:11]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH2:10]1)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[CH3:21]N(C=O)C.[OH-].[K+].IC>C1COCC1>[CH2:2]([N:9]1[CH2:14][CH2:13][C:12](=[O:15])[C:11]([CH3:21])([C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH2:10]1)[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1

Komponenten

6

Edukt 4

HCID 6228DimethylformamideHCID 6328Methyl iodideHCID 14797Potassium HydroxideHCID 102623Ethyl 1-benzyl-4-oxopiperidine-3-carboxylate hydrochloride

Produkt 1

HCID 14666544Ethyl 1-benzyl-3-methyl-4-oxopiperidine-3-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a suspension of ethyl 1-benzyl-4-oxopiperidine-3-carboxylate hydrochloride (20 g, 67.2 mmol) in THF (130 mL)/DMF (130 mL) was added KOH (powder, 7.64 g, 136 mmol) at room temperature. The reaction mixture was stirred for 5-10 min, then added iodomethane (4.62 mL, 73.9 mmol) dropwise. The reaction mixture was further stirred for 3 h at room temperature and then quenched with water. The aqueous phase was extracted with diethyl ether twice. The organic phases were combined and washed with water, dried over Na2SO4, filtered and concentrated. The resulting residue was purified by silica gel flash chromatography (0-20% EtOAc/heptanes) to provide ethyl 1-benzyl-3-methyl-4-oxopiperidine-3-carboxylate. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.15-7.45 (m, 5H), 4.00-4.21 (m, 2H), 3.66 (d, J=13.39 Hz, 1H), 3.47 (d, J=13.39 Hz, 1H), 3.30 (dd, J=2.78, 11.62 Hz, 1H), 2.96-3.08 (m, 1H), 2.77 (ddd, J=6.69, 11.68, 14.46 Hz, 1H), 2.36-2.45 (m, 1H), 2.27-2.35 (m, 1H), 2.14 (d, J=11.37 Hz, 1H), 1.15 (t, J=7.07 Hz, 3H), 1.09 (s, 3H).

Aufarbeitung

  1. stirringThe reaction mixture was further stirred for 3 h at room temperature
  2. customquenched with water
  3. extractionThe aqueous phase was extracted with diethyl ether twice
  4. washwashed with water
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe resulting residue was purified by silica gel flash chromatography (0-20% EtOAc/heptanes)

Quellen und Nachweise

ORD-Eintrag
ord-6279ed0557b14bc58f220b1ef01c0a2d
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08846656B2

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