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

HRID 21485

Reaction equation

HRID 21485 reaction equation
[F:1][C:2]1[C:7](O)=[C:6]([Cl:9])[CH:5]=[CH:4][C:3]=1[NH:10]C(=O)OC.C1(C)C=CC(S([O:24][CH:25]2[CH2:30][CH2:29][CH2:28][CH2:27][CH2:26]2)(=O)=O)=CC=1.[OH-].[K+].Cl>CN(C)C=O>[F:1][C:2]1[CH:7]=[C:6]([Cl:9])[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]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 13722Cyclohexyl p-toluenesulfonateHCID 14797Potassium HydroxideHCID 19374487Methyl N-(2-fluoro-4-chloro-hydroxyphenyl)carbamate

Product 1

HCID 152793952-Fluoro-4-chloro-5-cyclohexyloxyanilineYield 25.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

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×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, and the solvent was distilled off under reduced pressure to obtain a etude 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, 264 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.

Workup

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

Sources & evidence

ORD record
ord-ae085bb969d044aa842f7371fef80b29
Source dataset
uspto-grants-1995_06
Patent number
US05424277

Linked notes

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