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

Participants

Reaction Steps

To a solution of 2-phenylpiperazine (4.0 gram, 24.65 mmol) in dry CH2 Cl2 (200 ml) at -78 ° C. under nitrogen was added Et3N (5.15 ml, 36.97 mmol) followed by the dropwise addition of a CH2 Cl2 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 gel chromatography (150 g), eluting with 2.5% MeOH/CH2Cl2 to give (+,-) 1-[[3,5-bis(trifluoromethyl)phenyl]methyl]-3-phenyl-piperazine (6.96 gram, 17.92 mmol, 72.7%) as an oil. A portion of this oil (0.5 gram, 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 mass [M+1]+ 389; Found, C, 48.83; H, 4.28; N, 5.87; Cl, 14.77; F, 24.03. Calcd. for C19H18N2 F6.2HCl.0.25 H2O, C, 48.99; H, 4.43; N, 6.01; Cl, 15.22; F, 24.47.

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