3,4,5,6-Tetrahydrophthalic anhydride → 2-(4-Chloro-2-fluorophenyl)-4,5,6,7-tetrahydro-1h-isoindole-1,3(2h)-dione

HRID 437703Notes

Reaction equation

HRID 437703 reaction equation
[C:1]1(=[O:11])[O:6][C:4](=O)[C:3]2[CH2:7][CH2:8][CH2:9][CH2:10][C:2]1=2.[Cl:12][C:13]1[CH:19]=[CH:18][C:16]([NH2:17])=[C:15]([F:20])[CH:14]=1>C(O)(=O)C>[Cl:12][C:13]1[CH:19]=[CH:18][C:16]([N:17]2[C:1](=[O:11])[C:2]3[CH2:10][CH2:9][CH2:8][CH2:7][C:3]=3[C:4]2=[O:6])=[C:15]([F:20])[CH:14]=1

Participants

4

Reactant 2

HCID 124753,4,5,6-Tetrahydrophthalic anhydrideHCID 938984-Chloro-2-fluoroaniline

Product 1

HCID 1859312-(4-Chloro-2-fluorophenyl)-4,5,6,7-tetrahydro-1h-isoindole-1,3(2h)-dione

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A solution of 88 parts of 3,4,5,6-tetrahydrophthalic anhydride in 2000 parts of glacial acetic acid was treated with 84 parts of 4-chloro-2-fluoroaniline at once and stirred for one hour. After refluxing for 19 hours, 1000 parts of acetic acid were distilled from the reaction mixture. The residue from the distillation was poured over 3000 parts of ice. The resulting crystals were filtered and recrystallized from 700 parts of methanol at -40° C. after activated carbon treatment, to yield 117 parts off-white crystals of 2-(4-chloro-2-fluorophenyl)-4,5,6,7-tetrahydro-2H-isoindole-1,3-dione melting at 76.5°-78.0° C.

Workup

  1. temperatureAfter refluxing for 19 hours
  2. distillation1000 parts of acetic acid were distilled from the reaction mixture
  3. distillationThe residue from the distillation
  4. additionwas poured over 3000 parts of ice
  5. filtrationThe resulting crystals were filtered
  6. customrecrystallized from 700 parts of methanol at -40° C. after activated carbon treatment

Sources & evidence

ORD record
ord-eaf704beb3c24ebaad8b8545d5d6ef48
Source dataset
uspto-grants-1977_06
Patent number
US04032326

Reaction notes

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