Cesium carbonate → Ethyl 4-[4-[4-(7-methoxyheptyloxy)-3,5-dimethylphenyl]piperazin-1-yl]benzoate

HRID 1816727Notes

Reaction equation

HRID 1816727 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[N:53]1([C:59]2[CH:69]=[CH:68][C:62]([C:63]([O:65][CH2:66][CH3:67])=[O:64])=[CH:61][CH:60]=2)[CH2:58][CH2:57][NH:56][CH2:55][CH2:54]1.Br[C:71]1[CH:72]=[C:73]([CH3:88])[C:74]([O:78][CH2:79][CH2:80][CH2:81][CH2:82][CH2:83][CH2:84][CH2:85][O:86][CH3:87])=[C:75]([CH3:77])[CH:76]=1>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:87][O:86][CH2:85][CH2:84][CH2:83][CH2:82][CH2:81][CH2:80][CH2:79][O:78][C:74]1[C:73]([CH3:88])=[CH:72][C:71]([N:56]2[CH2:55][CH2:54][N:53]([C:59]3[CH:60]=[CH:61][C:62]([C:63]([O:65][CH2:66][CH3:67])=[O:64])=[CH:68][CH:69]=3)[CH2:58][CH2:57]2)=[CH:76][C:75]=1[CH3:77]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 2761178Ethyl 4-(piperazin-1-yl)benzoateHCID 224947715-Bromo-2-(7-methoxyheptyloxy)-1,3-dimethylbenzene

Product 1

HCID 22494740Ethyl 4-[4-[4-(7-methoxyheptyloxy)-3,5-dimethylphenyl]piperazin-1-yl]benzoateYield 36.2%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent2×

Procedure

To a mixture of cesium carbonate (1.39 g), palladium(II) acetate (34.1 mg) and 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (142 mg) in toluene (3.1 ml) was successively added ethyl 4-(piperazin-1-yl)benzoate (0.85 g) and a solution of 5-bromo-2-(7-methoxyheptyloxy)-1,3-dimethylbenzene (1.00 g) in toluene (3 ml) in a stream of nitrogen. The mixture was stirred at ambient temperature for 30 minutes and refluxed for a further 20 hours. After cooling, the reaction mixture was concentrated in vacuo and to the residue was added water and methylene chloride. The organic layer was separated, washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified by silica gel column chromatography eluting successively with the following solvent: (1) n-hexane, (2) n-hexane;ethyl acetate=9:1, (3) n-hexane:ethyl acetate=5:1. The fractions containing the object compound were concentrated in vacuo to give ethyl 4-[4-[4-(7-methoxyheptyloxy)-3,5-dimethylphenyl]piperazin-1-yl]benzoate (0.53 g) as a pale yellow solid.

Workup

  1. temperaturerefluxed for a further 20 hours
  2. temperatureAfter cooling
  3. concentrationthe reaction mixture was concentrated in vacuo and to the residue
  4. additionwas added water and methylene chloride
  5. customThe organic layer was separated
  6. washwashed with saturated aqueous sodium chloride solution
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by silica gel column chromatography
  11. washeluting successively with the following solvent
  12. additionThe fractions containing the object compound
  13. concentrationwere concentrated in vacuo

Sources & evidence

ORD record
ord-324bb4f462a34a89afea68997ad38c1a
Source dataset
uspto-grants-2005_04
Patent number
US06884868B1

Reaction notes

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