Hippuric Acid → N-{2-Oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazine-1-yl]-ethyl}benzamide

HRID 1178079Notes

Reaction equation

HRID 1178079 reaction equation
CCN(C(C)C)C(C)C.[C:10]([NH:18][CH2:19][C:20]([OH:22])=O)(=[O:17])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.Cl.[N:46]1([C:52]([C:54]2[CH:59]=[CH:58][CH:57]=[CH:56][C:55]=2[C:60]([F:63])([F:62])[F:61])=[O:53])[CH2:51][CH2:50][NH:49][CH2:48][CH2:47]1>CN(C=O)C.O>[O:22]=[C:20]([N:49]1[CH2:50][CH2:51][N:46]([C:52](=[O:53])[C:54]2[CH:59]=[CH:58][CH:57]=[CH:56][C:55]=2[C:60]([F:63])([F:61])[F:62])[CH2:47][CH2:48]1)[CH2:19][NH:18][C:10](=[O:17])[C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1

Participants

8

Reactant 5

HCID 464Hippuric AcidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 167337831-(2-Trifluoromethylbenzoyl)piperazine hydrochloride

Product 1

HCID 59559588N-{2-Oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazine-1-yl]-ethyl}benzamideYield 30%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (0.169 mL, 0.98 mmol) was added to a stirred solution of benzoylamino-acetic acid (50 mg, 0.28 mmol) in DMF (1 mL). HOBT (45 mg, 0.34 mmol) and EDCI.HCl (64 mg, 0.34 mmol) were added followed by the addition of piperazine-1-yl-(2-trifluoromethyl-phenyl)-methanone hydrochloride (0.31 mmol) at room temperature. The resulting mixture was stirred at room temperature overnight. Water was then added, and the product was extracted with EtOAc. The organic layer was washed with brine, dried over Na2SO4 and concentrated under reduced pressure to afford the crude product. Purification using column chromatography (using silica gel, 60-120 A° and 10% methanol in chloroform as the eluent) afforded N-{2-Oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazine-1-yl]-ethyl}benzamide in 30% yield, LC-MS purity: 95%, 1H NMR (CDCl3): δ 7.84 (d, 2H), 7.76 (d, 1H), 7.66-7.56 (m, 2H), 7.54-7.42 (m, 3H), 7.34 (d, 2H), 7.24 (t, 1H), 4.36-4.20 (m, 2H), 4.02-3.84 (m, 2H), 3.78-3.50 (m, 4H), 3.26 (m, 2H).

Workup

  1. extractionthe product was extracted with EtOAc
  2. washThe organic layer was washed with brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customto afford the crude product
  6. customPurification

Sources & evidence

ORD record
ord-ca6ed1019bef4faf962090e7c081e2ab
Source dataset
uspto-grants-2010_11
Patent number
US07842696B2

Reaction notes

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