Trifluoroacetic acid → 5-Bromo-4-methylisobenzofuran-1(3H)-one

HRID 2281282Notes

Reaction equation

HRID 2281282 reaction equation
[Br:1][C:2]1[C:3]([CH3:10])=[C:4]([CH2:8][OH:9])[CH:5]=[CH:6][CH:7]=1.FC(F)(F)[C:13](O)=[O:14].FC(F)(F)C([O-])=O.[Tl+].[Cl-].[Li+].[O-2].[Mg+2]>[Pd](Cl)Cl.CO>[Br:1][C:2]1[CH:7]=[CH:6][C:5]2[C:13](=[O:14])[O:9][CH2:8][C:4]=2[C:3]=1[CH3:10]

Participants

8

Reactant 5

HCID 6422Trifluoroacetic acidHCID 433294Lithium ChlorideHCID 6850729Magnesium monoxideHCID 10035697(3-Bromo-2-methylphenyl)methanolHCID 21902506Thallium(1+);2,2,2-trifluoroacetate

Product 1

HCID 595687115-Bromo-4-methylisobenzofuran-1(3H)-one

Reagents, catalysts & solvents 2

HCID 24290Palladium ChlorideCatalystHCID 887MethanolSolvent

Procedure

To a flask charged with (3-bromo-2-methylphenyl)methanol (6.0 g, 30 mmol) was added a 1M trifluoroacetic acid solution of thallium trifluoroacetate (16.2 g, 29.8 mmol). The mixture was stirred at RT overnight. The solvent was removed under vacuum, and the residue was pumped under high vacuum for 30 minutes to ensure complete removal of TFA. To the residue was then added palladium (II) chloride (529 mg, 2.98 mmol), lithium chloride (2.53 g, 59.7 mmol), magnesium oxide (2.41 g, 59.7 mmol), and methanol (150 mL). The reaction was flushed with CO twice, and kept under CO at room temperature. Analysis by LC showed a big product spot within 2 hours. To this solution was added ethyl acetate to precipitate the salts. The black solution was filtered through a Celite® pad, washed with EtOAc, adsorbed onto silica and purified by silica gel chromatography to afford 5-bromo-4-methyl-2-benzofuran-1 (3H)-one. 1H-NMR (500 MHz, CDCl3) δ ppm 7.71 (d, J=8.0 Hz, 1H), 7.58 (d, J=8.0 Hz, 1H), 5.25 (s, 2H), 2.37 (s, 3H).

Workup

  1. customThe solvent was removed under vacuum
  2. waitthe residue was pumped under high vacuum for 30 minutes
  3. customremoval of TFA
  4. customThe reaction was flushed with CO twice
  5. customkept under CO at room temperature
  6. customwithin 2 hours
  7. additionTo this solution was added ethyl acetate
  8. customto precipitate the salts
  9. filtrationThe black solution was filtered through a Celite® pad
  10. washwashed with EtOAc
  11. custompurified by silica gel chromatography

Sources & evidence

ORD record
ord-582f401fef2d4cf3bc6b112329f0c4bc
Source dataset
uspto-grants-2015_09
Patent number
US09139585B2

Reaction notes

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