Water → N-(2-fluoro-4-chloro-5-methoxycarbonyloxyphenyl)-3,4,5,6-tetrahydrophthalimide

HRID 128546Notes

Reaction equation

HRID 128546 reaction equation
[F:1][C:2]1[CH:8]=[C:7]([Cl:9])[C:6]([O:10][C:11]([O:13][CH3:14])=[O:12])=[CH:5][C:3]=1[NH2:4].[C:15]1(=O)[O:20][C:18](=[O:19])[C:17]2[CH2:21][CH2:22][CH2:23][CH2:24][C:16]1=2.O>C(O)(=O)C>[F:1][C:2]1[CH:8]=[C:7]([Cl:9])[C:6]([O:10][C:11]([O:13][CH3:14])=[O:12])=[CH:5][C:3]=1[N:4]1[C:18](=[O:19])[C:17]2[CH2:21][CH2:22][CH2:23][CH2:24][C:16]=2[C:15]1=[O:20]

Participants

5

Reactant 3

HCID 962WaterHCID 124753,4,5,6-Tetrahydrophthalic anhydrideHCID 107989305-Amino-2-chloro-4-fluorophenyl methyl carbonate

Product 1

HCID 19374481N-(2-fluoro-4-chloro-5-methoxycarbonyloxyphenyl)-3,4,5,6-tetrahydrophthalimideYield 79.2%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A solution of 2-fluoro-4-chloro-5-methoxycarbonyloxyaniline (20.0 g, 91.1 mmol) and 3,4,5,6-tetrahydrophthalic anhydride (14.0 g, 92.0. mmol) in acetic acid (200 ml) was reacted for 5 hours while heating under refluxing. After completion of the reaction, the mixture was cooled to room temperature, water (200 ml) was added thereto, and extracted with ethyl acetate (100 ml×3 times). The organic layer was washed with an aqueous solution of sodium carbonate and water, dried, and the solvent was distilled off under reduced pressure. The resulting oily substance was purified by silica gel column chromatography (development solvent: ethyl acetate/hexane=1/5) to obtain N-(2-fluoro-4-chloro-5-methoxycarbonyloxyphenyl)-3,4,5,6-tetrahydrophthalimide as a white solid (26.2 g, 72.1 mmol, 79.2% yield).

Workup

  1. temperaturewhile heating
  2. temperatureunder refluxing
  3. customAfter completion of the reaction
  4. extractionextracted with ethyl acetate (100 ml×3 times)
  5. washThe organic layer was washed with an aqueous solution of sodium carbonate and water
  6. customdried
  7. distillationthe solvent was distilled off under reduced pressure
  8. customThe resulting oily substance was purified by silica gel column chromatography (development solvent: ethyl acetate/hexane=1/5)

Sources & evidence

ORD record
ord-6f834f5b7b94400dbbe17015277f855e
Source dataset
uspto-grants-1995_11
Patent number
US05464811

Reaction notes

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