Triethylamine → 1-{[3,5-Bis(trifluoromethyl)phenyl]methyl}-3-phenylpiperazine

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Reaction Steps

To a solution of 2-phenylpiperazine (4.0 g, 24.65 mmol) in dry CH2Cl2 (200 mL) at -78° C. under nitrogen was added Et3N (5.15 mL, 36.97 mmol) followed by the dropwise addition of a CH2Cl2 solution(46.60 mL) of bis(trifluoromethyl)benzyl bromide (4.66 mL, 24.65 mmol). The flask was kept at -78° C. then it was gradually warmed to room temperature overnight. After TLC showed that the reaction was complete, the material was washed with brine (150 mL, 2×), dried over MgSO4, filtered, and evaporated under vacuum to yield a tan solid. The crude product was purified by flash silica get chromatography (150 g), eluting with 2.5% MeOH/CH2Cl2 to give (+,-) 1-[[3,5-bis(trifluoromethyl)phenyl]methyl]-3-phenylpiperazine (6.96 g, 17.92 mmol, 72.7%) as an oil. A portion of this oil (0.5 g, 1.287 mmol)) was converted to its hydrochloride salt by dissolving the oil in CH2Cl2 (20 mL) and treating with 2.3M HCl-EtOH (1.3 mL 2.99 mmol). After stirring at room temperature for 10 minutes, all solvents were removed under high vacuum and the residue was dried overnight, m.p. 229°-233° C.; FAB MS [M+1]+ 389;

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