Potassium Carbonate → 1-(3-fluorobenzyl)-5-nitro-1H-indazole

HRID 38510

Reaction equation

HRID 38510 reaction equation
[N+:1]([C:4]1[CH:5]=[C:6]2[C:10](=[CH:11][CH:12]=1)[NH:9][N:8]=[CH:7]2)([O-:3])=[O:2].C(=O)([O-])[O-].[K+].[K+].[F:19][C:20]1[CH:21]=[C:22]([CH:25]=[CH:26][CH:27]=1)[CH2:23]Br>C1COCC1>[F:19][C:20]1[CH:21]=[C:22]([CH:25]=[CH:26][CH:27]=1)[CH2:23][N:9]1[C:10]2[C:6](=[CH:5][C:4]([N+:1]([O-:3])=[O:2])=[CH:12][CH:11]=2)[CH:7]=[N:8]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 215015-NitroindazoleHCID 680073-Fluorobenzyl bromide

Product 1

HCID 219664901-(3-fluorobenzyl)-5-nitro-1H-indazoleYield 35.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

5-Nitroindazol (10.0 g, 61.3 mmol) was dissolved in THF (100 mL). Potassium carbonate (25.4 g, 184 mmol) and 3-fluorobenzylbromide (12.7 g, 67.4 mmol) were added, and the mixture was heated to reflux for 3 h. The solvent was removed in vacuo, and the residue was dissolved in ethyl acetate (150 mL) and extracted with water (200 mL). The aqueous layer was extracted twice with ethyl acetate (100 mL each). The combined organic layers were dried over sodium sulfate, and the solvent was removed in vacuo. The residue was purified by column chromatography on silica gel (eluent: cyclohexane/ethyl acetate 3:1) to yield 6.55 g (39%) of the title compound (less polar component) and 5.84 g (35%) of the regioisomeric 2H-indazole derivative (more polar component).

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux for 3 h
  3. customThe solvent was removed in vacuo
  4. dissolutionthe residue was dissolved in ethyl acetate (150 mL)
  5. extractionextracted with water (200 mL)
  6. extractionThe aqueous layer was extracted twice with ethyl acetate (100 mL each)
  7. dry with materialThe combined organic layers were dried over sodium sulfate
  8. customthe solvent was removed in vacuo
  9. customThe residue was purified by column chromatography on silica gel (eluent: cyclohexane/ethyl acetate 3:1)

Sources & evidence

ORD record
ord-eced96baf29e45a89f35dbfc2d2f9206
Source dataset
uspto-grants-2013_09
Patent number
US08524722B2

Linked notes

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