Acetic Acid → [1-(1-(p-Bromobenzyl)-5-methoxy-2-methylindol-3-yl)-cyclopropyl]acetonitrile

Participants

Reaction Steps

To a 0° C. mixture of the ketone from Step 4 (920 mg, 6.71 mmol) and the hydrazine from Step 5 (2.15 g, 7.0 mmol) in 35 mL toluene was added acetic acid (0.97 mL, 17 mmol). The mixture was warmed to room temperature and stirred 1 h, then concentrated to dryness. The residue was dissolved in toluene and heptane and concentrated again and the process repeated until there was no more acetic acid remaining. The residue was then dissolved in 30 mL dioxane and treated with HCl (4M solution in dioxane, 4 mL, 16 mmol). The mixture was heated to 60° C. for 1.5 h, then cooled and partitioned between water and ethyl acetate. The organic phase was washed with saturated NaHCO3 and brine, dried over MgSO4 and evaporated. Purification by flash chromatography (15% ethyl acetate/hexanes) provided 2.32 g of the title compound.

Provenance & Evidence