Water → 4-Bromo-3-methyl-1H-indole

Participants

Reaction Conditions

Reaction Steps

To a solution of 4-bromo-1H-indole-3-carbaldehyde (7.5 g, 66.9 mmol) in THF (125 mL) was added LiAlH4 (40 mL, 1.0 M THF) dropwise at rt. The mixture was then heated at reflux for 2 h and was then cooled to 0° C. At that point 15% NaOH (2 mL) and water (7 mL) were added in sequence and the mixture was stirred vigorously for 1 h. At that point the suspension was filtered over Celite® and the filtrate was concentrated to provide crude 4-bromo-3-methyl-1H-indole, which was taken to the next step. A solution of crude 4-bromo-3-methyl-1H-indole (14.0 g, 66.9 mmol) in THF (50 mL) was added to a suspension of NaH (2.94 g, 73.6 mmol, 60% in mineral oil) in THF (200 mL) at 0° C. The mixture was stirred for 0.5 h at that temperature before a solution of p-toluene sulfonylcholoride (13.4 g, 70.2 mmol) in THF (50 mL) was added. After stirring for an additional 1 h sat aq NH4Cl was added slowly. The reaction mixture was then diluted with EtOAc and sat aq NH4Cl and the layers were separated. The organic layer was dried (Na2SO4), filtered and concentrated. The residue was then purified by FCC (0-50% EtOAc/heptane) to give 4-bromo-3-methyl-1-tosyl-1H-indole.

Provenance & Evidence