Acetic Acid → N-(2-Fluoro-4-chloro-5-cyclohexyloxyphenyl)-3,4,5,6-tetrahydrophthalimide

HRID 21467

Reaction equation

HRID 21467 reaction equation
[F:1][C:2]1[CH:8]=[C:7]([Cl:9])[C:6]([O:10][CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]2)=[CH:5][C:3]=1[NH2:4].[C:17]1(=O)[O:22][C:20](=[O:21])[C:19]2[CH2:23][CH2:24][CH2:25][CH2:26][C:18]1=2.C(O)(=O)C>O>[F:1][C:2]1[CH:8]=[C:7]([Cl:9])[C:6]([O:10][CH:11]2[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]2)=[CH:5][C:3]=1[N:4]1[C:20](=[O:21])[C:19]2[CH2:23][CH2:24][CH2:25][CH2:26][C:18]=2[C:17]1=[O:22]

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 124753,4,5,6-Tetrahydrophthalic anhydrideHCID 152793952-Fluoro-4-chloro-5-cyclohexyloxyaniline

Product 1

HCID 13604754N-(2-Fluoro-4-chloro-5-cyclohexyloxyphenyl)-3,4,5,6-tetrahydrophthalimideYield 70%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

2-Fluoro-4-chloro-5-cyclohexyloxyaniline (213 mg, 0.874 mmol), 3,4,5,6-tetrahydrophthalic anhydride (134 mg, 0.874 mmol) and acetic acid (10 ml) were charged into a 50 cc round-bottom flask, and heated for 15 hours while refluxing. After completion of the reaction, the reaction solution was cooled to room temperature, water (50 ml) was added thereto, and 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 separated by filtration and the solvent was distilled off under reduced pressure to obtain a crude product (332 mg). The product was purified by silica gel column chromatography (development solvent: hexane/ethyl acetate=19/1) to obtain N-(2-fluoro-4-chloro-5-cyclohexyloxyphenyl)-3,4,5,6-tetrahydrophthalimide as a white solid (230 mg, 0.609 mmol, 70% yield). By recrystallization of the product from hexane/chloroform, it was isolated as white needle crystals.

Workup

  1. temperatureheated for 15 hours
  2. temperaturewhile refluxing
  3. customAfter completion of the reaction
  4. extractionextracted with ethyl acetate (20 ml×3)
  5. washwashed with water
  6. dry with materiala saturated aqueous solution of sodium chloride, and dried over anhydrous magnesium sulfate
  7. customThe drying agent was separated by filtration
  8. distillationthe solvent was distilled off under reduced pressure
  9. customto obtain a crude product (332 mg)
  10. customThe product was purified by silica gel column chromatography (development solvent: hexane/ethyl acetate=19/1)

Sources & evidence

ORD record
ord-8524438ddfcb463cbe6b5acc30b921b7
Source dataset
uspto-grants-1995_06
Patent number
US05424277

Linked notes

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