Indole → Tetrahydrocyclopent(b)indole

참여 물질

반응 단계

In Step B, (R,S)-2-(3-oxo-cyclopentyl)-isoindole-1,3-dione (1) is reacted with 4-cyano-phenylhydrazine in a typical Fischer indole synthesis to give a tetrahydrocyclopenta[b]indole of formula (2). The skilled artisan will recognize that there are a variety of acidic conditions to effect a Fischer indole synthesis, including both proton and Lewis acids. The preferred conditions use a mixture of glacial acetic acid with 4 N HCl in dioxane, at a temperature of about 50° C. to the reflux temperature of the solvent, for about 4 to 24 hours. The product is isolated by addition of water followed by filtration of the resulting solid. The solid is sonicated in methanol to give material of sufficient purity. Alternatively, the reaction is effected using a Lewis acid, such as zinc chloride, in an amount of about 2 to 4 equivalents. Other preferred conditions for Step B use ethanol at reflux temperature for about 4 to 24 hours. The product is isolated and may be purified by filtration of the reaction mixture, followed by silica gel chromatography of the filtrate.

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