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

HRID 443062Notes

Reaction equation

HRID 443062 reaction equation
[C:1]1([CH:7]2[CH2:12][NH:11][CH2:10][CH2:9][NH:8]2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.CCN([CH2:18][CH3:19])CC.F[C:21]([C:24](Br)([C:31]([F:34])([F:33])[F:32])[C:25]1[CH:30]=[CH:29]C=CC=1)(F)F>C(Cl)Cl>[F:32][C:31]([F:34])([F:33])[C:30]1[CH:29]=[C:18]([CH2:19][N:11]2[CH2:10][CH2:9][NH:8][CH:7]([C:1]3[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=3)[CH2:12]2)[CH:21]=[C:24]([C:31]([F:32])([F:33])[F:34])[CH:25]=1

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 2506732-PhenylpiperazineHCID 18002160HCID 18002160, compound

Product 1

HCID 196101861-{[3,5-Bis(trifluoromethyl)phenyl]methyl}-3-phenylpiperazineYield 145.4%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

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;

Workup

  1. customwas kept at -78° C.
  2. washthe material was washed with brine (150 mL, 2×)
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. customevaporated under vacuum
  6. customto yield a tan solid
  7. customThe crude product was purified by flash silica
  8. customget chromatography (150 g)
  9. washeluting with 2.5% MeOH/CH2Cl2

Sources & evidence

ORD record
ord-e23f5d0e74f3466c8b4248a7f8bb2cc6
Source dataset
uspto-grants-1999_04
Patent number
US05892039

Reaction notes

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