Isatin → N-[3-(4-benzyloxyphenyl)phenyl]isatin

HRID 277349

Reaction equation

HRID 277349 reaction equation
[NH:1]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:4](=[O:5])[C:2]1=[O:3].[H-].[Na+].[CH2:14]([O:21][C:22]1[CH:27]=[CH:26][C:25]([C:28]2[CH:33]=[CH:32][CH:31]=[C:30](Br)[CH:29]=2)=[CH:24][CH:23]=1)[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>CN(C=O)C.[Cu](I)I>[CH2:14]([O:21][C:22]1[CH:23]=[CH:24][C:25]([C:28]2[CH:29]=[C:30]([N:1]3[C:11]4[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=4)[C:4](=[O:5])[C:2]3=[O:3])[CH:31]=[CH:32][CH:33]=2)=[CH:26][CH:27]=1)[C:15]1[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=1

Participants

6

Reactant 3

HCID 7054IsatinHCID 24758Sodium hydrideHCID 186833604-(3-Bromophenyl)phenol benzyl ether

Product 1

HCID 22016446N-[3-(4-benzyloxyphenyl)phenyl]isatin

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
140 °C

Procedure

Isatin (0.12 g, 0.81 mmol) in anhydrous DMF (30 mL) was cooled in an ice-bath under nitrogen and treated with sodium hydride (21 mg, 1.1 equivalents). The reaction was stirred in ice for 0.5 hours and then warm ed to room temperature. This solution was then treated with 4-(3-bromophenyl)phenol benzyl ether (Hajduk et al. Am. Chem. Soc. 1997, 119, 5818-5827), (0.16 g, 0.47 mmol) followed by copper iodide (0.32 g, 1.68 mmol). The reaction was heated in an oil-bath at 140° C. After ˜16 hours, the reaction was cooled to room temperature and concentrated under reduced pressure. The residue was dissolved in ethyl acetate (˜75 mL) and filtered. The filtrate was concentrated under reduced pressure to afford a sticky, brown solid which was purified by preparative TLC on silica gel using 25% ethyl acetate in hexanes as the developing solvent. Rf (product)=0.38. Yield =47 mg (25%); MADI-TOF MS 407.02 obs. (405.5 calc.); 1H-NMR (CDCl3) 5.12 (s, 2H), 6.95 (d, 1H, J=8 Hz), 7.06 (d, 2H, J=8.8 Hz), 7.18 (t, 1H, J=7.5 Hz), 7.33-7.47 (m, 7H), 7.53 (d, 2H, J=8.8 Hz), 7.57-7.60 (m, 2H), 7.71 (d, 1H, J=7.5 Hz).

Workup

  1. temperaturewarm
  2. customed to room temperature
  3. waitAfter ˜16 hours
  4. temperaturethe reaction was cooled to room temperature
  5. concentrationconcentrated under reduced pressure
  6. dissolutionThe residue was dissolved in ethyl acetate (˜75 mL)
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated under reduced pressure
  9. customto afford a sticky, brown solid which
  10. customwas purified by preparative TLC on silica gel using 25% ethyl acetate in hexanes as the developing solvent
  11. customYield =47 mg (25%)

Sources & evidence

ORD record
ord-03aed4214e004d90921e05d446198034
Source dataset
uspto-grants-2002_03
Patent number
US06355803B1

Linked notes

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