1,2-Difluoro-4-nitrobenzene → 6-bromo-5-(2-fluoro-4-nitrophenoxy)-1H-indazole

HRID 1661971Notes

Reaction equation

HRID 1661971 reaction equation
[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][NH:8]2)=[CH:4][C:3]=1[OH:11].[F:12][C:13]1[CH:14]=[C:15]([N+:20]([O-:22])=[O:21])[CH:16]=[CH:17][C:18]=1F.C([O-])(O)=O.[Na+].[Li+].[Cl-]>CN(C=O)C.C(Cl)Cl>[Br:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[N:7][NH:8]2)=[CH:4][C:3]=1[O:11][C:18]1[CH:17]=[CH:16][C:15]([N+:20]([O-:22])=[O:21])=[CH:14][C:13]=1[F:12]

Participants

7

Reactant 4

HCID 1230531,2-Difluoro-4-nitrobenzeneHCID 433294Lithium ChlorideHCID 516892Sodium BicarbonateHCID 591599466-Bromo-1H-indazol-5-ol

Product 1

HCID 667671536-bromo-5-(2-fluoro-4-nitrophenoxy)-1H-indazoleYield 50.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 6-bromo-5-hydroxy-1H-indazole (7.0 g, 33.0 mmol), 3,4-difluoronitrobenzene (4.98 mg, 31.0 mmol), NaHCO3 (2.5 g, 31.0 mmol) in DMF (100 mL) is stirred at 80° C. for 4 hours. Then LiCl (10% aqueous solution) is added and the solution is extracted with EtOAc. The organic phase is dried over anhydrous MgSO4, filtered and concentrated. The residue is purified by silica gel column chromatography eluting with PE:DCM (1:1) to give the desired product (5.5 g, 46.6% yield). MS (m/z): 354.0 (M+H).

Workup

  1. extractionthe solution is extracted with EtOAc
  2. dry with materialThe organic phase is dried over anhydrous MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue is purified by silica gel column chromatography
  6. washeluting with PE

Sources & evidence

ORD record
ord-2834e9e657a443aabaa3f6184b648543
Source dataset
uspto-grants-2011_10
Patent number
US08030302B2

Reaction notes

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