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

HRID 128552

反応式

HRID 128552 の反応式
[F:1][C:2]1[CH:7]=[C:6]([Cl:8])[C:5]([OH:9])=[CH:4][C:3]=1[NH:10][C:11](=[O:14])[O:12][CH3:13].[C:15]1(C)[CH:20]=[CH:19][C:18](S([O:24][CH:25]2[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]2)(=O)=O)=[CH:17][CH:16]=1.C(=O)([O-])[O-].[K+].[K+].Cl>[I-].[K+].CN(C)C=O>[F:1][C:2]1[CH:7]=[C:6]([Cl:8])[C:5]([O:9][CH:15]2[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]2)=[CH:4][C:3]=1[NH:10][C:11](=[O:14])[O:12][CH3:13].[F:1][C:2]1[CH:7]=[C:6]([Cl:8])[C:5]([O:24][CH:25]2[CH2:26][CH2:27][CH2:28][CH2:29][CH2:30]2)=[CH:4][C:3]=1[NH2:10]

参加物

8

反応物 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 13722Cyclohexyl p-toluenesulfonateHCID 19042327methyl N-(2-fluoro-4-chloro-5-hydroxyphenyl)carbamate

生成物 2

HCID 152793952-Fluoro-4-chloro-5-cyclohexyloxyaniline収率 19%HCID 19374473methyl N-(2-fluoro-4-chloro-5-cyclohexyloxyphenyl)carbamate収率 8.1%

試薬・触媒・溶媒 2

HCID 4875Potassium Iodide溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
80 °C

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 m 8.1% yield), 2-fluoro-4-chloro-5-cyclohexyloxyaniline (213 mg, 0.87 mmol, 19% yield) and the unreacted starting material, methyl N-(2-fluoro-4-chloro-5-hydroxyphenyl)-carbamate (540 mg, 2.48 mmol, 54% recovery ratio). [Methyl N-(2-fluoro-4-chloro-5-cyclohexyloxyphenyl)carbamate]

後処理

  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×3)
  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 (875 mg)
  9. customThe product was isolated
  10. custompurified by silica gel column chromatography (development solvent: hexane/ethyl acetate=9/1)

出典と根拠

ORDレコード
ord-f8effa636aa044499303a312c891d3a4
出典データセット
uspto-grants-1995_11
特許番号
US05464811

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