Ethanol → Ethyl 4-(piperazin-1-yl)benzoate

HRID 270769Notes

Reaction equation

HRID 270769 reaction equation
Br[C:2]1[CH:10]=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[CH:4][CH:3]=1.S(=O)(=O)(O)O.[NH:16]1[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]1.C(=O)([O-])[O-].[K+].[K+].[I-].[K+].[CH2:30](O)[CH3:31]>CCCC[N+](CCCC)(CCCC)CCCC.[I-].CN(C=O)C>[CH2:30]([O:8][C:6](=[O:7])[C:5]1[CH:9]=[CH:10][C:2]([N:16]2[CH2:21][CH2:20][NH:19][CH2:18][CH2:17]2)=[CH:3][CH:4]=1)[CH3:31]

Participants

9

Reactant 6

HCID 702EthanolHCID 1118Sulfuric AcidHCID 4837PiperazineHCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 114644-Bromobenzoic acid

Product 1

HCID 2761178Ethyl 4-(piperazin-1-yl)benzoate

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

To 4-bromobenzoic acid (25 g) and ethanol (1000 mL) was added conc.sulfuric acid (20 g) drop wise. The reaction mixture was heated at 85° C. overnight. The reaction was cooled and ethanol was removed by distillation and the reaction mixture quenched with water and extracted with ethyl acetate. The extract was washed with 10% sodium bicarbonate, water, brine and then concentrated to yield the crude ester. 4-bromoethyl benzoate (10.0 g, 0.0437 mol) was taken into 250 mL of dry DMF, piperazine (37 g, 0.437 mol) was added, followed by 30 g (0.2185 mol) of dry potassium carbonate, 1.0 g of TBAI and 1.5 g of potassium iodide. The reaction mixture was heated at 135° C. for over night. The reaction mixture was quenched with water and extracted with ethyl acetate. The extracts were washed with water, then brine and then concentrated to yield 4-Piperazin-1-yl-benzoic acid ethyl ester as an off-white solid.

Workup

  1. temperatureThe reaction was cooled
  2. customethanol was removed by distillation
  3. customthe reaction mixture quenched with water
  4. extractionextracted with ethyl acetate
  5. washThe extract was washed with 10% sodium bicarbonate, water, brine
  6. concentrationconcentrated
  7. customto yield the crude ester
  8. additionwas added
  9. temperatureThe reaction mixture was heated at 135° C. for over night
  10. customThe reaction mixture was quenched with water
  11. extractionextracted with ethyl acetate
  12. washThe extracts were washed with water
  13. concentrationbrine and then concentrated

Sources & evidence

ORD record
ord-508e216829a24e26862ec96a9f1cbe0d
Source dataset
uspto-grants-2008_11
Patent number
US07449576B1

Reaction notes

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