Trifluoroacetic acid → Methyl 3-(piperazin-1-yl)benzoate

HRID 1157162Notes

Reaction equation

HRID 1157162 reaction equation
C(O[C:6]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)=O)(C)(C)C.[CH3:14][O:15][C:16](=[O:24])[C:17]1[CH:22]=C[CH:20]=[C:19](Br)[CH:18]=1.C(P(C(C)(C)C)C1C=CC=CC=1C1C=CC=CC=1)(C)(C)C.CC(C)([O-])C.[Na+].C(O)(C(F)(F)F)=O>C1(C)C=CC=CC=1>[CH3:14][O:15][C:16](=[O:24])[C:17]1[CH:18]=[CH:19][CH:20]=[C:6]([N:8]2[CH2:9][CH2:10][NH:11][CH2:12][CH2:13]2)[CH:22]=1

Participants

7

Reactant 5

HCID 6422Trifluoroacetic acidHCID 12070Methyl 3-bromobenzoateHCID 143452tert-Butyl piperazine-1-carboxylateHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 23676156Sodium t-butoxide

Product 1

HCID 18930727Methyl 3-(piperazin-1-yl)benzoateYield 52.5%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a mixture containing piperazine-1-carboxylic acid tert-butyl ester (400 mg, 2.16 mmol), 3-bromo-benzoic acid methyl ester (547 mg, 2.56 mmol), Pd(AcO) (32 mg, 0.14 mmol), 2-(di-t-butylphosphino)biphenyl (80 mg, 0.28 mmol) and sodium t-butoxide (400 mg, 4 mmol) in toluene (20 mL) was degassed with Ar. The reaction mixture was heated at 50 C for overnight. At the end of reaction, ethyl acetate was added and the mixture was filter through celite. After removal of solvent, TFA was added to the residue. The reaction mixture was stirred at ambient temperature for 1 hour. The excess TFA was removed under vacuum and the residue was purified using prep-HPLC to give desired product (250 mg, 37% yield for two steps) as TFA salt.

Workup

  1. customwas degassed with Ar
  2. temperatureThe reaction mixture was heated at 50 C for overnight
  3. customAt the end of reaction, ethyl acetate
  4. additionwas added
  5. filtrationthe mixture was filter through celite
  6. customAfter removal of solvent, TFA
  7. additionwas added to the residue
  8. customThe excess TFA was removed under vacuum
  9. customthe residue was purified

Sources & evidence

ORD record
ord-c0c3a34054e14a23b21b3756a377dcd7
Source dataset
uspto-grants-2010_10
Patent number
US07807672B2

Reaction notes

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