Sodium Hydroxide → 1-(2-Tert-butylphenyl)piperazine

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Reaction Steps

A solution of 2-tert-butylaniline (35.7 g, 0.240 mol) and di(2-chloroethyl)amine hydrochloride (47.0 g, 0.264 mol) in diethylene glycol dimethyl ether (350 mL) was refluxed for 12 h. Then the mixture was cooled to room temperature, and 2 M NaOH solution (50 mL) was added. The mixture was extracted with ether, the combined organic layer was dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure to give crude product as a colorless oil. The product was purified by re-crystallization in petroleum ether to afford 1-[2-(tert-butyl)phenyl]piperazine (22.6 g, 43%) as a white solid. To the mixture of [2-(tert-butyl)phenyl]piperazine and ethyl acetate was added dropwise 4 M HCl solution in ethyl acetate (50 mL), keeping stirring for 0.5 h. Then the resulting solid was collected by filtration to give 1-[2-(tert-butyl)phenyl]piperazine dihydrochloride (30 g, quant.) as a white solid, which was re-crystallized in ethanol to give 1-(2-tert-butylphenyl)piperazine dihydrochloride.

Provenance & Evidence