Ethyl Acetate → 5-bromo-N-(4-methoxybenzyl)-3-methylindazole

HRID 490090Notes

Reaction equation

HRID 490090 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][N:6]=[C:5]2[CH3:11].CC(C)([O-])C.[K+].[CH3:18][O:19][C:20]1[CH:27]=[CH:26][C:23]([CH2:24]Cl)=[CH:22][CH:21]=1.C(OCC)(=O)C>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([CH2:24][C:23]1[CH:26]=[CH:27][C:20]([O:19][CH3:18])=[CH:21][CH:22]=1)[N:6]=[C:5]2[CH3:11]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 699934-Methyloxybenzyl chlorideHCID 23665647Potassium tert-butoxideHCID 178434225HCID 178434225, compound

Product 1

HCID 690009085-bromo-N-(4-methoxybenzyl)-3-methylindazoleYield 98.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 5-bromo-3-methylindazole 104 (0.2 g, 0.948 mmol) in anhydrous THF (3 mL), cooled in ice bath, was added potassium t-butoxide (0.127 g, 1.13 mmol) and 4-methoxybenzyl chloride (0.14 mL, 1.04 mmol). The reaction mixture was allowed to warmed to room temperature and was stirred for 16 hours. Ethyl acetate (100 mL) was added and the organic layer was washed with saturated ammonium chloride solution, water and brine. The organic layer was dried over sodium sulfate. The organic solvent was evaporated under reduced pressure. The crude product was purified by flash column chromatography to yield the desired 5-bromo-N-(4-methoxybenzyl)-3-methylindazole 105 (0.29 g, 0.932 mmol) as a mixture of the 1H- and 2H-indazole regioisomers.

Workup

  1. washthe organic layer was washed with saturated ammonium chloride solution, water and brine
  2. dry with materialThe organic layer was dried over sodium sulfate
  3. customThe organic solvent was evaporated under reduced pressure
  4. customThe crude product was purified by flash column chromatography

Sources & evidence

ORD record
ord-76fa1e9c32a94730a41a1a14409bf5da
Source dataset
uspto-grants-2009_05
Patent number
US07528132B2

Reaction notes

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