Citric Acid → HCID 86641942, Verbindung

Temperatur

100 °C

To a solution of 6-chloro-3-fluoropyridin-2-carboxylic acid methyl ester (245 mg) in dimethylformamide (3 ml), 200 mg of phenol and 393 mg of potassium carbonate were added, and the reaction solution was stirred at 100° C. for 1.5 hours. The reaction solution was cooled, then 1N hydrochloric acid was added, and the mixture was extracted with ethyl acetate. The combined organic layers were washed with a saturated saline solution and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to afford a crude product as a brown oil. To a solution of the crude product in toluene (5 ml), 9.9 ml of diisobutylaluminum hydride (1.0M hexane solution) was added at −78° C., and the reaction solution was stirred for 2 hours while increasing the temperature of the reaction solution to room temperature. To the reaction solution were added water and 10% aqueous citric acid sequentially, and the mixture was extracted with ethyl acetate. The combined organic layers were washed with a saturated saline solution and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and the residue obtained was purified by silica gel column chromatography (eluent: hexane/ethyl acetate (98:2-50:50)) to afford the title compound as a pale yellow oil.

1. temperatureThe reaction solution was cooled
2. extractionthe mixture was extracted with ethyl acetate
3. washThe combined organic layers were washed with a saturated saline solution
4. dry with materialdried over anhydrous sodium sulfate
5. distillationThe solvent was distilled off under reduced pressure
6. customto afford a crude product as a brown oil
7. stirringthe reaction solution was stirred for 2 hours
8. temperaturewhile increasing the temperature of the reaction solution to room temperature
9. extractionthe mixture was extracted with ethyl acetate
10. washThe combined organic layers were washed with a saturated saline solution
11. dry with materialdried over anhydrous sodium sulfate
12. distillationThe solvent was distilled off under reduced pressure
13. customthe residue obtained
14. customwas purified by silica gel column chromatography (eluent: hexane/ethyl acetate (98:2-50:50))

ORD-Eintrag

ord-14d89ee2882e4809af2adf771bbc64fd

Quelldatensatz

uspto-grants-2013_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08367708B2