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

HRID 21484

반응식

HRID 21484 반응식
[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]

참가 물질

8

반응물 4

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

생성물 2

HCID 152793952-Fluoro-4-chloro-5-cyclohexyloxyanilineHCID 19374473methyl N-(2-fluoro-4-chloro-5-cyclohexyloxyphenyl)carbamate수율 8.1%

시약·촉매·용매 2

HCID 4875Potassium Iodide용매HCID 6228Dimethylformamide용매

반응 조건

온도
80 °C

실험 절차

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

후처리

  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)

출처 및 근거

ORD 기록
ord-3d4427abd9114c99ba4001a2231dd2c4
출처 데이터셋
uspto-grants-1995_06
특허 번호
US05424277

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