4-Methyloxybenzyl chloride → 5-Bromo-1-(4-methoxybenzyl)-1H-indazole

HRID 1911891Notes

Reaction equation

HRID 1911891 reaction equation
CC([O-])(C)C.[K+].[Br:7][C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[NH:13][N:12]=[CH:11]2.[CH3:17][O:18][C:19]1[CH:26]=[CH:25][C:22]([CH2:23]Cl)=[CH:21][CH:20]=1>C1COCC1>[Br:7][C:8]1[CH:9]=[C:10]2[C:14](=[CH:15][CH:16]=1)[N:13]([CH2:23][C:22]1[CH:25]=[CH:26][C:19]([O:18][CH3:17])=[CH:20][CH:21]=1)[N:12]=[CH:11]2

Participants

5

Reactant 3

HCID 699934-Methyloxybenzyl chlorideHCID 7619295-bromo-1H-indazoleHCID 23665647Potassium tert-butoxide

Product 1

HCID 442405275-Bromo-1-(4-methoxybenzyl)-1H-indazole

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a suspension of KOtBu (8.13 g, 72.4 mmol) in THF (60 mL) was added 5-bromo-1H-indazole (12.98 g, 65.9 mmol) in THF (60 mL). After 30 min, 4-methoxybenzyl chloride (9.38 mL, 69.2 mmol) was added (neat) and the resulting pale yellow solution was stirred 48 h. The reaction was quenched by addition of saturated NH4Cl solution, and the mixture was extracted with EtOAc. Evaporation of the organic phase followed by column chromatography of the residue on silica gel, eluting with 1/9-EtOAc/heptane, afforded the title compound, which was recrystallized from toluene/heptane (1/5) to afford the title compound as colorless cubes (7.65 g, 37%). Also recovered from the chromatography was 5-bromo-2-(4-methoxybenzyl)-2H-indazole (8.0 g, 38%)

Workup

  1. customThe reaction was quenched by addition of saturated NH4Cl solution
  2. extractionthe mixture was extracted with EtOAc
  3. customEvaporation of the organic phase
  4. washeluting with 1/9-EtOAc/heptane

Sources & evidence

ORD record
ord-69e3211d911a401b887ecff797ab6198
Source dataset
uspto-grants-2013_12
Patent number
US08604205B2

Reaction notes

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