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

HRID 1396682Notes

Reaction equation

HRID 1396682 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+].C1OCCOCCOCCOCCOCCOC1.[N:44](OCCC(C)C)=O>C(Cl)(Cl)Cl.CCOC(C)=O>[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:44]=[CH:13]2

Participants

8

Reactant 5

HCID 7918Acetic AnhydrideHCID 8053Isoamyl NitriteHCID 2855718-Crown-6HCID 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 6212ChloroformSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of N-(4-bromo-5-fluoro-2-methylphenyl)acetamide (29B, 10.00 g, 40.64 mmol) in chloroform (100 mL) was treated with acetic anhydride (11.5 mL, 122.0 mmol), potassium acetate (8.00 g, 81.5 mmol), and 18-Crown-6 (540.00 mg, 2.0430 mmol) and then with isoamyl nitrite (12.3 mL, 871 mmol) and heated at 65° C. for 12 hours. The reaction mixture was cooled to room temperature and treated with EtOAc (500 mL), washed with water, dried (MgSO4), filtered, and then concentrated in vacuo. A pale yellow solid of 1-(5-bromo-6-fluoro-1H-indazol-1-yl)ethanone (29C) precipitated out. The initial filtrate was concentrated and the residue was purified using chromatography (SiO2, EtOAc/Hexanes) to yield more of product 29C.

Workup

  1. washwashed with water
  2. dry with materialdried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. customA pale yellow solid of 1-(5-bromo-6-fluoro-1H-indazol-1-yl)ethanone (29C) precipitated out
  6. concentrationThe initial filtrate was concentrated
  7. customthe residue was purified

Sources & evidence

ORD record
ord-432d5b3b1d7f4a2886b45c13e1dec143
Source dataset
uspto-grants-2014_12
Patent number
US08901139B2

Reaction notes

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