Acetic Acid → ethyl 8-chloro-1-cyclopropyl-9-difloromethoxy-4-oxo-4H-quinolizine-3-carboxylate

Temperatur

100 °C

71.6 mg of 2-(4-chloro-3-difluoromethyl-2-pyridyl)-2-cyclopropylethanal (XII) was dissolved in 3 ml of anhydrous ethanol, to which were added 80 μl of piperidine, 80 μl of acetic acid and 220 μl of diethyl malonate and the resulting mixture was heated at 100° C. for 5 hours. The solvent was distilled off by under reduced pressure, and thereafter, the resulting mixture was diluted with ether, and the resulting organic layer was washed with water and saturated salt water, and dried over anhydrous sodium sulfate, and the solvent was distilled off by under reduced pressure. 2 ml of Dowtherm A was added to the resulting residue, and the resulting mixture was heated at 240° C. for 30 minutes. The reaction solution was purified directly by silica gel column chromatography (eluent; hexane→hexane:ethyl acetate=1:1) to obtain 51.3 mg of ethyl 8-chloro-1-cyclopropyl-9-difluoromethyl-4-oxo-4H-quinolidine-3-carboxylate (XIII).

1. distillationThe solvent was distilled off by under reduced pressure
2. additionthe resulting mixture was diluted with ether
3. washthe resulting organic layer was washed with water and saturated salt water
4. dry with materialdried over anhydrous sodium sulfate
5. distillationthe solvent was distilled off by under reduced pressure
6. addition2 ml of Dowtherm A was added to the resulting residue
7. temperaturethe resulting mixture was heated at 240° C. for 30 minutes
8. customThe reaction solution was purified directly by silica gel column chromatography (eluent; hexane→hexane:ethyl acetate=1:1)

ORD-Eintrag

ord-0acbdaf5af694cf1a602544723511eb4

Quelldatensatz

uspto-grants-2003_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06525066B2