Reaktion #220018

Reaktionsgleichung

enamine

1-Benzyl-4-pyrrolidino-1,2,5,6-tetrahydropyridine

ethyl 2-(ethoxymethylene)-4,4,4-trifluoro-3-oxobutyrate

Ammonium acetate

→

title compound

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

Lösungsmittel

1,4-dioxane

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturthe mixture was heated
2. 2
   Temperaturat reflux for 2 h
3. 3
   Temperaturcooled to room temperature
4. 4
   Einengenconcentrated under reduced pressure
5. 5
   SonstigeThe residue was partitioned between ether and water
6. 6
   Waschenthe ether layer was washed with saturated brine
7. 7
   Trocknendried over magnesium sulfate
8. 8
   Einengenconcentrated to a red oil
9. 9
   SonstigePurification by flash chromatography (silica gel; 12% ethyl acetate/hexanes as eluant)

Vorschrift

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).

Quelle