N-(2-Hydroxyethyl)phthalimide → 2-{2-[(4-Bromo-phenyl)-(4-chloro-phenyl)-methoxy]-ethyl}-isoindole-1,3-dione

HRID 888596Notes

Reaction equation

HRID 888596 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:10]2[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][CH:11]=2)[OH:9])=[CH:4][CH:3]=1.O[CH2:18][CH2:19][N:20]1[C:24](=[O:25])[C:23]2=[CH:26][CH:27]=[CH:28][CH:29]=[C:22]2[C:21]1=[O:30].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:10]2[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][CH:11]=2)[O:9][CH2:18][CH2:19][N:20]2[C:21](=[O:30])[C:22]3[C:23](=[CH:26][CH:27]=[CH:28][CH:29]=3)[C:24]2=[O:25])=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 77499N-(2-Hydroxyethyl)phthalimideHCID 521998p-Toluenesulfonic acid monohydrateHCID 57659206(4-Bromophenyl)(4-chlorophenyl)methanol

Product 1

HCID 593319222-{2-[(4-Bromo-phenyl)-(4-chloro-phenyl)-methoxy]-ethyl}-isoindole-1,3-dioneYield 56.3%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A mixture of (4-Bromo-phenyl)-(4-chloro-phenyl)-methanol (2.3 g, 7.73 mmol), N-(2-hydroxyethyl)phthalimide (1.4 g, 7.36 mmol) and para-toluenesulphonic acid monohydrate (560 mg, 2.94 mmol) in toluene (50 ml) was heated to reflux under Dean-Stark conditions for 17 hours. Upon cooling, the solvent was removed and the residue was partitioned between ethyl acetate and water. The organic layer was then dried (MgSO4), filtered and concentrated. The crude product was purified by column chromatography (SiO2), eluting with ethyl acetate/petroleum ether (1:4), to yield the title compound (1.95 g). LC/MS: (PS-B3) R1 4.07 no observable mass ion.

Workup

  1. temperaturewas heated
  2. temperatureto reflux under Dean-Stark conditions for 17 hours
  3. temperatureUpon cooling
  4. customthe solvent was removed
  5. customthe residue was partitioned between ethyl acetate and water
  6. dry with materialThe organic layer was then dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude product was purified by column chromatography (SiO2)
  10. washeluting with ethyl acetate/petroleum ether (1:4)

Sources & evidence

ORD record
ord-ba424da7aab54723850ac71300d94124
Source dataset
uspto-grants-2012_08
Patent number
US08247576B2

Reaction notes

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