Sodium Iodide → 1-[2-(2,2,2-Trifluoroethoxy)phenyl]piperazine

Participants

Reaction Steps

A mixture of 2-(2,2,2-trifluoroethoxy)aniline (3.89 g, 20.4 mmol), bis(2-chloroethyl)amine hydrochloride (3.64 g, 20.4 mmol), potassium carbonate (2.82 g, 20.4 mmol) and sodium iodide (0.6 g, 4.1 mmol) in 10 mL of 2-methoxyethyl ether was heated at reflux for 4.5 hours. The mixture was cooled and 20 mL of an aqueous solution at pH 9 was added. The mixture was extracted with ethyl acetate (4×50 mL) and the combined organic layers were washed with brine, dried (Na2SO4) and concentrated. The residue was purified on silica gel by column chromatography eluting with 5% methanol/methylene chloride to give 1-[2-(2,2,2-trifluoroethoxy)phenyl]piperazine (2.74 g, 10.6 mmol). The free base was recrystallized from hydrochloric acid in alcohol to give 1-[2-(2,2,2-trifluoroethoxy)phenyl]piperazine hydrochloride, m.p. 172°-173° C.

Provenance & Evidence