تفاعل #49762

معادلة التفاعل

potassium carbonate

Methyl N-(2-fluoro-4-chloro-5-hydroxyphenyl)carbamate

hydrochloric acid

cyclohexyl p-toluenesulfonate

→

methyl N-(2-fluoro-4-chloro-5-cyclohexyloxyphenyl)carbamate

المردود 8.1%

2-fluoro-4-chloro-5-cyclohexyloxyaniline

المذيبات

potassium iodide

N,N-dimethylformamide

ظروف التفاعل

المعالجة

1. 1
   أخرىAfter completion of the reaction
2. 2
   درجة الحرارةthe reaction solution was cooled to room temperature
3. 3
   استخلاصthe mixture was extracted with ethyl acetate (20 ml×3)
4. 4
   غسيلwashed with water
5. 5
   تجفيفa saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate
6. 6
   أخرىThe drying agent was removed by filtration
7. 7
   workup.DISTILLATIONthe solvent was distilled off under reduced pressure
8. 8
   أخرىto obtain a crude product (875 mg)
9. 9
   أخرىThe product was isolated
10. 10
    أخرىpurified by silica gel column chromatography (development solvent: hexane/ethyl acetate=9/1)

الإجراء التجريبي

Methyl N-(2-fluoro-4-chloro-5-hydroxyphenyl)carbamate (1.00 g, 4.56 mmol) synthesized by the process described in Reference Example 3, cyclohexyl p-toluenesulfonate (1.20 g, 4.73 mmol), potassium carbonate (635 mg, 4.95 mmol), a catalytic amount of potassium iodide and N,N-dimethylformamide (20 ml) as a solvent were charged into a 100 cc round-bottom flask, and stirred 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×3). 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, the solvent was distilled off under reduced pressure to obtain a crude product (875 mg). The product was isolated and purified by silica gel column chromatography (development solvent: hexane/ethyl acetate=9/1) to obtain methyl N-(2-fluoro-4-chloro-5-cyclohexyloxyphenyl)carbamate (12 mg, 0.46 mmol, 8.1% yield), 2-fluoro-4-chloro-5-cyclohexyloxyaniline (213 mg, 0.87 mmol, 194 yield) and the unreacted starting material, methyl N-(2-fluoro-4-chloro-5-hydroxyphenyl)carbamate (540 mg, 2.46 mmol, 544 recovery ratio). [Methyl N-(2-fluoro-4-chloro-5-cyclohexyloxyphenyl)carbamate] White needle crystals

المصدر