Ethanol → 1-[2-[Bis(4-fluorophenyl)methoxy]ethyl]-4-(phenylmethyl)piperazine maleate

HRID 2286361Notes

Reaction equation

HRID 2286361 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([C:18]2[CH:23]=[CH:22][C:21]([F:24])=[CH:20][CH:19]=2)[O:9][CH2:10][CH2:11][N:12]2[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]2)=[CH:4][CH:3]=1.[C:25](=[O:28])([O-:27])[O-].[K+].[K+].[CH2:31](Br)[C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1.C([OH:41])C>>[C:8]([OH:41])(=[O:9])/[CH:18]=[CH:23]\[C:25]([OH:27])=[O:28].[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]([C:18]2[CH:19]=[CH:20][C:21]([F:24])=[CH:22][CH:23]=2)[O:9][CH2:10][CH2:11][N:12]2[CH2:17][CH2:16][N:15]([CH2:31][C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[CH2:14][CH2:13]2)=[CH:6][CH:7]=1

Participants

5

Reactant 4

HCID 702EthanolHCID 7498Benzyl Bromide2×HCID 11430Potassium CarbonateHCID 99740131-[2-[Bis(4-fluorophenyl)methoxy]ethyl]piperazine

Product 1

HCID 705735041-[2-[Bis(4-fluorophenyl)methoxy]ethyl]-4-(phenylmethyl)piperazine maleate

Procedure

To a mixture of 6 g (0.018 mol) of 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]piperazine (prepared as described in Example 3) and 3 g of potassium carbonate powder in 50 ml of ethanol, 3.1 g (0.018) of benzylbromide were added dropwise at room temperature. The reaction mixture was then slowly heated and refluxed for 3 hours. Subsequently another 3.1 g (0.018 mol) of benzylbromide were added dropwise at room temperature. The mixture was refluxed for 1,5 hours, cooled and filtered. The solvent was distilled off and the residue was purified by column chromatography (silicagel) with a mixture of chloroform and ethyl acetate (1:1) as the eluent. A solvent of maleic acid in diethyl ether was added to the desired eluate fraction, the precipitate was filtered off and crystallized from a mixture of methanol and dimethylformamide. 1-[2-[Bis(4-fluorophenyl)methoxy]ethyl]-4-(phenylmethyl)piperazine maleate (1:2) was obtained. Melting point 201.5°-202.5° C.

Workup

  1. additionwere added dropwise at room temperature
  2. temperatureThe reaction mixture was then slowly heated
  3. temperaturerefluxed for 3 hours
  4. temperatureThe mixture was refluxed for 1,5 hours
  5. temperaturecooled
  6. filtrationfiltered
  7. distillationThe solvent was distilled off
  8. customthe residue was purified by column chromatography (silicagel) with a mixture of chloroform and ethyl acetate (1:1) as the eluent
  9. additionA solvent of maleic acid in diethyl ether was added to the desired eluate fraction
  10. filtrationthe precipitate was filtered off
  11. customcrystallized from a mixture of methanol and dimethylformamide

Sources & evidence

ORD record
ord-7f925aa57b554748a9a1e08d0aa9bd60
Source dataset
uspto-grants-1981_05
Patent number
US04265894

Reaction notes

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