Sodium Hydroxide → 5-Bromo-4-fluoro-1H-indazole

HRID 2069555Notes

Reaction equation

HRID 2069555 reaction equation
[Br:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[C:4]([CH3:9])[C:3]=1[F:10].[N:11]([O-])=O.[Na+].[OH-].[Na+]>CC(O)=O>[Br:1][C:2]1[C:3]([F:10])=[C:4]2[C:5](=[CH:7][CH:8]=1)[NH:6][N:11]=[CH:9]2

Participants

5

Reactant 3

HCID 14798Sodium HydroxideHCID 157466844-Bromo-3-fluoro-2-methylanilineHCID 23668193Sodium Nitrite

Product 1

HCID 454803935-Bromo-4-fluoro-1H-indazoleYield 75.9%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Procedure

To a solution of 4-bromo-3-fluoro-2-methylaniline (20 g, 98.0 mmol) in CH3CO2H (600 mL) was added NaNO2 (8.1 g, 118 mmol) at 10° C. The resulting mixture was stirred at room temperature for 4 hours. Upon completion, aqueous NaOH (50%) was added to the reaction mixture until pH was ˜7-8. The mixture was extracted with EtOAc. The organic layer was dried over Na2SO4 and concentrated in vacuo. The residue was purified by column chromatography on silica gel (0˜40% EtOAc in petroleum ether) affording the title compound (16 g). 1H NMR (300 MHz, DMSO-d6): δ 13.58 (br, 1H), 8.22 (s, 1H), 7.53 (t, 1H), 7.38 (d, 1H).

Workup

  1. extractionThe mixture was extracted with EtOAc
  2. dry with materialThe organic layer was dried over Na2SO4
  3. concentrationconcentrated in vacuo
  4. customThe residue was purified by column chromatography on silica gel (0˜40% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-a382503f0b224b42b43432ec5fa060cd
Source dataset
uspto-grants-2012_10
Patent number
US08299112B2

Reaction notes

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