Dimethylamine → 1-(5-Chloro-1H-indol-3-yl)-N,N-dimethylmethanamine

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Reaction Steps

Aqueous dimethylamine (8.0 mL, 63.7 mmol) and aqueous formaldehyde (4.8 mL, 64.0 mL) were combined in dioxane (50 mL) and acetic acid (50 mL). 5-Chloro-1H-indole (9.5 g, 62.5 mmol) in dioxane (30 mL) was added dropwise to the mixture, which was then was stirred at room temperature for 18 hours. The mixture was concentrated to approximately 50 mL by rotary evaporation, diluted with water (≈500 mL), and extracted with ether (~200 mL). The aqueous phase was separated, cooled, made basic with sodium hydroxide, and extracted into methylene chloride. The methylene chloride phase was separated, washed with water and then brine, dried over potassium carbonate, filtered, and evaporated. Crystallization from a mixture of acetone and diisopropyl ether gave 3-(dimethylaminomethyl)-5-chloro-1H-indole (10.6 g, 50.5 mmol) as white crystals, m.p. 148°-150° C.

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