3,4,5,6-Tetrahydrophthalic anhydride → N-{2-fluoro-4-chloro-5-(2-methylcyclopentyl)oxyphenyl}-3,4,5,6-tetrahydrophthalimide

HRID 128536Notes

Reaction equation

HRID 128536 reaction equation
[F:1][C:2]1[CH:8]=[C:7]([Cl:9])[C:6]([O:10][CH:11]2[CH2:15][CH2:14][CH2:13][CH:12]2[CH3:16])=[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>[F:1][C:2]1[CH:8]=[C:7]([Cl:9])[C:6]([O:10][CH:11]2[CH2:15][CH2:14][CH2:13][CH:12]2[CH3:16])=[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

4

Reactant 2

HCID 124753,4,5,6-Tetrahydrophthalic anhydrideHCID 152793932-Fluoro-4-chloro-5-(2-methylcyclopentyl)oxyaniline

Product 1

HCID 15279394N-{2-fluoro-4-chloro-5-(2-methylcyclopentyl)oxyphenyl}-3,4,5,6-tetrahydrophthalimideYield 98%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

2-Fluoro-4-chloro-5- (2-methylcyclopentyl) oxyaniline (660 mg, 2.71 mmol), 3,4,5,6-tetrahydrophthalic anhydride (503 mg, 3.31 mmol) and acetic acid (10 ml) were charged into a 50 cc round-bottom flask, and heated for 5 hours while refluxing. After completion of the reaction, the reaction solution was cooled to room temperature, and poured into ice-water (100 ml). The mixture was extracted with ethyl acetate (30 ml×3), and 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, the solvent was distilled off under reduced pressure, and the resulting pale brown oily substance was purified by silica gel column chromatography (development solvent: hexane/ethyl acetate=9/1) to obtain N-{2-fluoro-4-chloro-5-(2-methylcyclopentyl)oxyphenyl}-3,4,5,6-tetrahydrophthalimide (1.00 g, 2.65 mmol, 98% yield)

Workup

  1. temperatureheated for 5 hours
  2. temperaturewhile refluxing
  3. customAfter completion of the reaction
  4. extractionThe mixture was extracted with ethyl acetate (30 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. customthe resulting pale brown oily substance was purified by silica gel column chromatography (development solvent: hexane/ethyl acetate=9/1)

Sources & evidence

ORD record
ord-d83e524fe4d54eb4b43de769e61e2090
Source dataset
uspto-grants-1995_11
Patent number
US05464811

Reaction notes

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