Trifluoroacetic acid → 4-Chloro-7-(1H-benzoimidazol-2-yl)isoindolinone

HRID 21118Notes

Reaction equation

HRID 21118 reaction equation
[Cl:1][C:2]1[CH:10]=[CH:9][C:8]([C:11]2[NH:15][C:14]3[CH:16]=[CH:17][CH:18]=[CH:19][C:13]=3[N:12]=2)=[C:7]2[C:3]=1[CH:4](O)[N:5](C(C)(C1C=CC=CC=1)C)[C:6]2=[O:20].FC(F)(F)C(O)=O.C([SiH](CC)CC)C.C(=O)([O-])O.[Na+]>[N+](C)([O-])=O.CCCCCC.C(OCC)(=O)C>[Cl:1][C:2]1[CH:10]=[CH:9][C:8]([C:11]2[NH:12][C:13]3[CH:19]=[CH:18][CH:17]=[CH:16][C:14]=3[N:15]=2)=[C:7]2[C:3]=1[CH2:4][NH:5][C:6]2=[O:20]

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acid3×HCID 12052Triethylsilane3×HCID 516892Sodium BicarbonateHCID 684917394-chloro-3-hydroxy-7-(1H-benzoimidazol-2-yl)-2-(1-methyl-1-phenylethyl)isoindolinone

Product 1

HCID 684903324-Chloro-7-(1H-benzoimidazol-2-yl)isoindolinoneYield 51.2%

Reagents, catalysts & solvents 2

HCID 6375NitromethaneSolventHCID 21226206Ethyl acetate hexaneSolvent

Procedure

4-Chloro-3-hydroxy-7-(1H-benzoimidazol-2-yl)-2-(1-methyl-1-phenylethyl)isoindolinone (39.4 mg, 0.0943 mmol) was dissolved in nitromethane (2.8 mL), and the solution was added with trifluoroacetic acid (0.073 mL, 0.94 mmol) and triethylsilane (0.030 mL, 0.19 mmol), followed by stirring at room temperature for 23.5 hours. Then, the mixture was added with trifluoroacetic acid (0.146 mL, 1.89 mmol) and triethylsilane (0.045 mL, 0.28 mmol) and warmed to 70° C., followed by stirring for 7.5 hours. Further, the mixture was added with trifluoroacetic acid (1.00 mL) and triethylsilane (0.15 mL, 0.94 mmol), followed by stirring for 4 hours. The reaction mixture was added with saturated aqueous sodium hydrogencarbonate solution and extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by slurry using chloroform/methanol (9/1) and by preparative thin-layer chromatography (hexane/ethyl acetate=2/1, 1/1) to obtain Compound 174 (13.7 mg, yield 51%).

Workup

  1. temperaturewarmed to 70° C.
  2. stirringby stirring for 7.5 hours
  3. stirringby stirring for 4 hours
  4. extractionextracted with ethyl acetate
  5. washThe organic layer was washed with saturated brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. customThe solvent was evaporated under reduced pressure
  8. customThe residue was purified by slurry

Sources & evidence

ORD record
ord-8f63c7309e0c4c93ab5188919adbf01a
Source dataset
uspto-grants-2010_06
Patent number
US07745641B2

Reaction notes

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