Ammonium Acetate → Ethyl 6-benzyl-2-(trifluoromethyl)-5,6,7,8-tetrahydro-1,6-naphthridine-3-carboxylate

HRID 132836Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 132836
[CH2:1]([N:8]1[CH2:13][CH2:12][C:11]([N:14]2CCCC2)=[CH:10][CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C(O[CH:22]=[C:23]([C:29](=O)[C:30]([F:33])([F:32])[F:31])[C:24]([O:26][CH2:27][CH3:28])=[O:25])C.C([O-])(=O)C.[NH4+]>O1CCOCC1>[CH2:1]([N:8]1[CH2:13][CH2:12][C:11]2[N:14]=[C:29]([C:30]([F:31])([F:32])[F:33])[C:23]([C:24]([O:26][CH2:27][CH3:28])=[O:25])=[CH:22][C:10]=2[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Komponenten

5

Edukt 3

HCID 517165Ammonium AcetateHCID 4685753Ethyl 2-(ethoxymethylene)-4,4,4-trifluoro-3-oxobutanoateHCID 117468121-Benzyl-4-(1-pyrrolidinyl)-1,2,3,6-tetrahydropyridine

Produkt 1

HCID 69193694Ethyl 6-benzyl-2-(trifluoromethyl)-5,6,7,8-tetrahydro-1,6-naphthridine-3-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 312751,4-DioxaneLösungsmittel

Versuchsvorschrift

A solution of the crude enamine (2.67 g, 10.6 mmol) from Step A above in 30 mL of dry 1,4-dioxane was cooled to approximately 10° C. and ethyl 2-(ethoxymethylene)-4,4,4-trifluoro-3-oxobutyrate (2.3 mL, 11.7 mmol) was added dropwise. The resultant orange solution was allowed to warm to room temperature overnight. Ammonium acetate (1.78 g) was added to the blood-red solution, and the mixture was heated at reflux for 2 h, cooled to room temperature and concentrated under reduced pressure. The residue was partitioned between ether and water, and the ether layer was washed with saturated brine, dried over magnesium sulfate and concentrated to a red oil. Purification by flash chromatography (silica gel; 12% ethyl acetate/hexanes as eluant) followed by preparative TLC (silica gel; 15% ethyl acetate/hexanes as eluant) afforded the title compound as a light yellow oil. LC/MS 365.2 (M+1).

Aufarbeitung

  1. temperaturethe mixture was heated
  2. temperatureat reflux for 2 h
  3. temperaturecooled to room temperature
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was partitioned between ether and water
  6. washthe ether layer was washed with saturated brine
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated to a red oil
  9. customPurification by flash chromatography (silica gel; 12% ethyl acetate/hexanes as eluant)

Quellen und Nachweise

ORD-Eintrag
ord-b60d3568ff054bd8b0e43e247f0ecb53
Quelldatensatz
uspto-grants-2008_06
Patentnummer
US07388019B2

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