反応 #49762

反応方程式

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

収率 8.1%

2-fluoro-4-chloro-5-cyclohexyloxyaniline

溶媒

potassium iodide

N,N-dimethylformamide

反応条件

後処理

1. 1
   その他After completion of the reaction
2. 2
   温度the reaction solution was cooled to room temperature
3. 3
   抽出the mixture was extracted with ethyl acetate (20 ml×3)
4. 4
   洗浄washed with water
5. 5
   乾燥a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate
6. 6
   その他The drying agent was removed by filtration
7. 7
   workup.DISTILLATIONthe solvent was distilled off under reduced pressure
8. 8
   その他to obtain a crude product (875 mg)
9. 9
   その他The product was isolated
10. 10
    その他purified by silica gel column chromatography (development solvent: hexane/ethyl acetate=9/1)

実験手順

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

出典