2-(Trifluoromethyl)benzoic acid → HCID 17683255, compound

HRID 1665586Notes

Reaction equation

HRID 1665586 reaction equation
C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.[F:20][C:21]([F:32])([F:31])[C:22]1[CH:30]=[CH:29][CH:28]=[CH:27][C:23]=1[C:24]([OH:26])=O.CCN=C=NCCCN(C)C.Cl.[CH2:45]([N:52]1[CH2:57][CH2:56][NH:55][CH2:54][CH2:53]1)[C:46]1[CH:51]=[CH:50][CH:49]=[CH:48][CH:47]=1>CN(C=O)C.O>[CH2:45]([N:52]1[CH2:57][CH2:56][N:55]([C:24]([C:23]2[CH:27]=[CH:28][CH:29]=[CH:30][C:22]=2[C:21]([F:20])([F:32])[F:31])=[O:26])[CH2:54][CH2:53]1)[C:46]1[CH:47]=[CH:48][CH:49]=[CH:50][CH:51]=1

Participants

8

Reactant 5

HCID 98992-(Trifluoromethyl)benzoic acidHCID 757711-HydroxybenzotriazoleHCID 759941-BenzylpiperazineHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride

Product 1

HCID 17683255HCID 17683255, compoundYield 93.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
10 °C

Procedure

HOBt (4.26 g, 31.5 mmol) and DIEA (10.19 g, 78.89 mmol) were added to a stirred solution of 2-trifluoromethylbenzoic acid (5 g, 26.3 mmol) in DMF (20 mL). The reaction mixture was cooled to 10° C. and EDCI.HCl (12.6 g, 65.7 mmol) followed by 1-benzyl-piperazine (5.56 g, 31.55 mmol) were then added. The reaction mixture was stirred at room temperature overnight, then diluted with water and the product extracted with ethyl acetate. The ethyl acetate was washed with brine solution, dried over Na2SO4 and evaporated. The resulting residue was purified by column chromatography using silica gel 60-120 mesh with (30% ethyl acetate in hexane) to afford 8.6 g (93%) of (4-benzyl-piperazin-1-yl)-(2-trifluoromethyl-phenyl)-methanone. 1H NMR: (DMSO-d6): δ 7.8 (m, 2H), 7.6 (t, 1H), 7.4 (d, 1H), 7.3 (m, 5H), 3.6 (m, 2H), 3.5 (s, 2H), 3.1 (m, 2H), 2.4 (m, 1H), 2.3 (m, 2H), 2.2 (m, 1H).

Workup

  1. additionwere then added
  2. extractionthe product extracted with ethyl acetate
  3. washThe ethyl acetate was washed with brine solution
  4. dry with materialdried over Na2SO4
  5. customevaporated
  6. customThe resulting residue was purified by column chromatography

Sources & evidence

ORD record
ord-f30f57c9886c4236bf4ae5cabfd66a18
Source dataset
uspto-grants-2011_10
Patent number
US08039463B2

Reaction notes

Loading…