1-(2-Methoxyphenyl)piperazine → 2-Hydroxy-N-{2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl}benzamide

HRID 638162Notes

Reaction equation

HRID 638162 reaction equation
[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[N:9]1[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]1.Br.[NH2:16][CH2:17][CH2:18]Br.C(=O)([O-])[O-].[K+].[K+].C([O:29][C:30]1[C:31](=[CH:35][CH:36]=[CH:37][CH:38]=1)[C:32](Cl)=[O:33])(=O)C>C(OCC)(=O)C.C(O)CCC>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=1[N:9]1[CH2:14][CH2:13][N:12]([CH2:18][CH2:17][NH:16][C:32](=[O:33])[C:31]2[CH:35]=[CH:36][CH:37]=[CH:38][C:30]=2[OH:29])[CH2:11][CH2:10]1

Participants

7

Reactant 4

HCID 13461-(2-Methoxyphenyl)piperazineHCID 11430Potassium CarbonateHCID 796682-Acetoxybenzoyl chlorideHCID 27742172-Bromoethylamine hydrobromide

Product 1

HCID 133184962-Hydroxy-N-{2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl}benzamideYield 50.1%

Reagents, catalysts & solvents 2

HCID 2631-ButanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

To 1.92 g (0.01 mol) of 1-(2-methoxyphenyl)piperazine, 2.05 g (0.01 mol) of 2-aminoethyl bromide hydrobromide, 2.76 g (0.02 mol) of anhydrous potassium carbonate and 40 ml of n-butanol were added, and the mixture was refluxed for 6 hours. After the reaction, the mixture was concentrated under vacuum, and to the resulting residue, 2.5 g of anhydrous sodium carbonate, 20 ml of water and 20 ml of ethyl acetate were added. Under agitation with cooling on ice, 2.38 g (0.012 mol) of acetylsalicylic acid chloride as dissolved in a small amount of ethyl acetate was added dropwise to the mixture. Thereafter, the mixture was stirred for 30 minutes under cooling with ice and extracted with ethyl acetate by agitation for 30 minutes at room temperature. The separated organic layer was washed with water, and 1N HCl was added until the pH became 3.0. The aqueous layer was separated, neutralized with sodium hydroxide and extracted with ethyl acetate. The resulting organic layer was washed with water, dried with Glauber's salt and concentrated under vacuum. The residue was subjected to column chromatography on silica gel (solvent: chloroform/methanol=100:1) to provide 1.78 g (yield: 50%) of 1-(2-methoxyphenyl)-4-[2-(2-hydroxybenzoyl)aminoethyl]piperazine as an oily substance.

Workup

  1. temperaturethe mixture was refluxed for 6 hours
  2. customAfter the reaction
  3. concentrationthe mixture was concentrated under vacuum
  4. additionto the resulting residue, 2.5 g of anhydrous sodium carbonate, 20 ml of water and 20 ml of ethyl acetate were added
  5. additionwas added dropwise to the mixture
  6. temperatureunder cooling with ice
  7. extractionextracted with ethyl acetate by agitation for 30 minutes at room temperature
  8. washThe separated organic layer was washed with water, and 1N HCl
  9. additionwas added until the pH
  10. customThe aqueous layer was separated
  11. extractionextracted with ethyl acetate
  12. washThe resulting organic layer was washed with water
  13. dry with materialdried with Glauber's salt
  14. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-de112b680cbe4ea398e0dbfab6b57480
Source dataset
uspto-grants-1985_12
Patent number
US04560686

Reaction notes

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