Methanol → 6-Hydroxymethylindole

Participants

Reaction Steps

A stirred solution of methyl indole-6-carboxylate (50 g) (see Example 1, part b) in dry toluene (1 liter), in a three-necked three-liter flask fitted with a mechanical stirrer, thermometer and dropping funnel, was cooled to -70° under an atmosphere of nitrogen, and treated dropwise with a solution of diisobutylaluminum hydride (381 ml of 1.5M solution in toluene) over 50 min. After 2.5 hr a further portion of diisobutylaluminum hydride (25 ml) was added dropwise, and the mixture stirred for a further 30 min. Methanol (100 ml) and saturated aqueous sodium sulfate (100 ml) were added sequentially, at -78°. The cooling bath was removed, the reaction allowed to warm to room temperature, and 6M hydrochloric acid (25 ml) was added dropwise. The mixture was filtered through a pad of diatomaceous earth, the filter cake washed with toluene and water, the organic phase separated and washed with water, dried (MgSO4) and evaporated to give 6-hydroxymethylindole (34.2 g, 82%) as an oil which slowly solidified; partial NMR (250 MHz, CDCl3): 1.73(s, 1H, CH2OH), 4.78(s, 2H, CH2OH), 6.55(m, 1H, H3 -indole), 8.20(br s, 1H, NH).

Provenance & Evidence