Hydrochloric Acid → 2-Fluoro-4-chloro-5-cyclohexyloxyaniline

Temperatur

80 °C

Methyl N-(2-fluoro-4-chloro-hydroxyphenyl)carbamate (2.03 g, 9.23 mmol), cyclohexyl p-toluenesulfonate (2.51 g, 9.85 mmol) and N,N-dimethylformamide (30 ml) were charged into a 100 cc round-bottom flask, and then potassium hydroxide (1.0 g, 17.8 mmol) in a powder form was added thereto. The mixture was stirred for 4 hours on an oil bath at 80° C. After completion of the reaction, the reaction solution was cooled to room temperature, 1N hydrochloric acid (100 ml) was added thereto, and the mixture was extracted with ethyl acetate (20 ml×8). The organic layers were combined, washed with water and a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate. The drying agent was removed by filtration, and the solvent was distilled off under reduced pressure to obtain a crude product. The product was isolated and purified by silica gel column chromatography (development solvent: hexane/ethyl acetate=9/1) to obtain 2-fluoro-4-chloro-5-cyclohexyloxyaniline (574 mg, 2.36 mmol, 26% yield) and the unreacted starting material, methyl N-(2-fluoro-4-chloro-5-hydroxyphenyl)carbamate (1.22 g, 5.54 mmol, 60% recovery ratio). The spectral data and the like are as shown in Reference Example 11.

1. customAfter completion of the reaction
2. temperaturethe reaction solution was cooled to room temperature
3. extractionthe mixture was extracted with ethyl acetate (20 ml×8)
4. washwashed with water
5. dry with materiala saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate
6. customThe drying agent was removed by filtration
7. distillationthe solvent was distilled off under reduced pressure
8. customto obtain a crude product
9. customThe product was isolated
10. custompurified by silica gel column chromatography (development solvent: hexane/ethyl acetate=9/1)

ORD-Eintrag

ord-6d697adb8b4a4cd7926d6414d8922467

Quelldatensatz

uspto-grants-1995_11

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US05464811