Acetic Anhydride → 1-(5-bromo-6-fluoro-1H-indazol-1-yl)ethanone

HRID 34127Notes

Reaction equation

HRID 34127 reaction equation
[Br:1][C:2]1[C:7]([F:8])=[CH:6][C:5]([NH:9][C:10](=[O:12])[CH3:11])=[C:4]([CH3:13])[CH:3]=1.C(OC(=O)C)(=O)C.C([O-])(=O)C.[K+].[N:26](OCCC(C)C)=O>C1(C)C=CC=CC=1.C(OCC)(=O)C>[Br:1][C:2]1[CH:3]=[C:4]2[C:5](=[CH:6][C:7]=1[F:8])[N:9]([C:10](=[O:12])[CH3:11])[N:26]=[CH:13]2

Participants

7

Reactant 4

HCID 7918Acetic AnhydrideHCID 8053Isoamyl NitriteHCID 517044Potassium AcetateHCID 23070217N-(4-Bromo-5-fluoro-2-methylphenyl)acetamide

Product 1

HCID 596944751-(5-bromo-6-fluoro-1H-indazol-1-yl)ethanone

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 77.0 g of N-(4-bromo-5-fluoro-2-methylphenyl)acetamide in 930 mL of toluene were added 93.0 mL of acetic anhydride and 37.0 g of potassium acetate at room temperature, and the resultant solution was heated at 90° C., slowly added dropwise with 67.0 mL of isoamyl nitrite, and stirred at this temperature for 3 hours. After diluting with ethyl acetate, washing successively with water and saturated brine, and drying over anhydrous magnesium sulfate, the solvent was evaporated. The precipitated crystals were washed with diethyl ether:n-hexane=1:10, the filtrate concentrated and purified and separated by silica gel column chromatography (ethyl acetate:n-hexane=0:100-1:5) and finally combined with the previous crystals, to afford 22.5 g of the title compound as pale brown crystals.

Workup

  1. washwashing successively with water and saturated brine
  2. dry with materialdrying over anhydrous magnesium sulfate
  3. customthe solvent was evaporated
  4. washThe precipitated crystals were washed with diethyl ether
  5. concentrationn-hexane=1:10, the filtrate concentrated
  6. custompurified
  7. customseparated by silica gel column chromatography (ethyl acetate:n-hexane=0:100-1:5)

Sources & evidence

ORD record
ord-e6dd642600d64666b6ac13e904e2c92b
Source dataset
uspto-grants-2008_09
Patent number
US07429609B2

Reaction notes

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