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

HRID 975777Notes

Reaction equation

HRID 975777 reaction equation
[Cl:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[C:4]([F:9])[CH:3]=1.[C:10]1(=O)[O:15][C:13](=[O:14])[C:12]2[CH2:16][CH2:17][CH2:18][CH2:19][C:11]1=2.O.C(OCC)(=O)C.C(OCC)(=O)C>C(O)(=O)C>[Cl:1][C:2]1[CH:8]=[CH:7][C:5]([N:6]2[C:10](=[O:15])[C:11]3[CH2:19][CH2:18][CH2:17][CH2:16][C:12]=3[C:13]2=[O:14])=[C:4]([F:9])[CH:3]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 124753,4,5,6-Tetrahydrophthalic anhydrideHCID 938984-Chloro-2-fluoroaniline2×HCID 22728543Water ethylacetate

Product 1

HCID 1859312-(4-Chloro-2-fluorophenyl)-4,5,6,7-tetrahydro-1h-isoindole-1,3(2h)-dioneYield 69.3%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

A mixture of 4-chloro-2-fluoroaniline (19.0 g, 130.6 mmol), and 3,4,5,6-tetrahydrophthalic anhydride (19.85 g, 130.6 mmol) in acetic acid (150 mL) is refluxed for 2 hours, treated with additional 4-chloro-2-fluoroaniline (3.0 g), refluxed for 90 minutes, stirred at room temperature overnight and poured into a water/ethyl acetate mixture. The organic phase is washed sequentially with water, saturated sodium hydrogen carbonate solution and brine, dried over anhydrous magnesium sulfate and concentrated in vacuo to obtain a purple oil. Flash column chromatography of the oil using silica gel and 15% to 20% ethyl acetate in hexanes solutions gives the title product as an off-white solid (25.3 g, mp 81°-82° C.).

Workup

  1. temperatureis refluxed for 2 hours
  2. temperaturerefluxed for 90 minutes
  3. washThe organic phase is washed sequentially with water, saturated sodium hydrogen carbonate solution and brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated in vacuo
  6. customto obtain a purple oil

Sources & evidence

ORD record
ord-82c94f50e6ba440692358528e940ad1b
Source dataset
uspto-grants-1997_03
Patent number
US05610120

Reaction notes

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