Iodine → 1-[1-(4-Bromophenyl)-1-methyl-ethyl]-piperidine

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Reaction Steps

In a three necked round bottom flask fitted with a condenser and nitrogen stream, was placed a small quantity of ground glass and magnesium turnings (190 mg, 7.40 mmol). The mixture was stirred for 30 minutes under vacuum then placed under nitrogen and iodine added (one small crystal), followed by the rapid addition of 1,4-dibromobenzene (2.43 g, 10.3 mmol) in 15 ml of anhydrous diethyl ether. The reaction mixture was then heated under reflux for 5 minutes. After this time, a solution of 1-(1-cyano-1-methylethyl)-piperidine (1.0 g, 6.60 mmol) in anhydrous THF was added dropwise resulting in the formation of a white precipitate. The reaction mixture was heated under reflux for 1.5 h, before cooling to ambient temperature. The resultant mixture was treated with saturated aqueous potassium carbonate solution and extracted with DCM. The organic extract was dried over magnesium sulfate and concentrated in vacuo. The crude residue was purified by column chromatography (silica, 12 g column, ISCO, 0-40% ethyl acetate in cyclohexane) to afford the title compound (200 mg, 95%) as a colourless oil. LCMS (Method B): RT=1.99 min, M+H+=282, 284.

Provenance & Evidence