3,5-Bis(trifluoromethyl)benzoic acid → N-[(2S)-2-(4-fluorophenyl)pent-4-en-1-yl]-N-methyl-3,5-bis(trifluoromethyl)benzamide

HRID 749452Notes

Reaction equation

HRID 749452 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C@H:8]([CH2:12][CH:13]=[CH2:14])[CH2:9][NH:10][CH3:11])=[CH:4][CH:3]=1.[F:15][C:16]([F:31])([F:30])[C:17]1[CH:18]=[C:19]([CH:23]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:25]=1)[C:20]([OH:22])=O.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F.CCN(C(C)C)C(C)C>CN(C=O)C.C([O-])(O)=O.[Na+]>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C@H:8]([CH2:12][CH:13]=[CH2:14])[CH2:9][N:10]([CH3:11])[C:20](=[O:22])[C:19]2[CH:23]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:25]=[C:17]([C:16]([F:15])([F:31])[F:30])[CH:18]=2)=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 128893,5-Bis(trifluoromethyl)benzoic acidHCID 81531DiisopropylethylamineHCID 2733207O-(Benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborateHCID 15536023[(2S)-2-(4-Fluorophenyl)pent-4-en-1-yl]methylamine

Product 1

HCID 86606886N-[(2S)-2-(4-fluorophenyl)pent-4-en-1-yl]-N-methyl-3,5-bis(trifluoromethyl)benzamideYield 85.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 516892Sodium BicarbonateSolvent

Procedure

[(2S)-2-(4-Fluorophenyl)pent-4-en-1-yl]methylamine (Bioorg. Med. Chem. Lett; 2001; 265-270; 300 mg, 1.55 mmol) was dissolved in DMF (3 mL) and to the resultant solution were added 3,5-bis(trifluoromethyl)benzoic acid (440 mg, 1.71 mmol), TBTU (548 mg, 1.71 mmol) and DIPEA (803 mg, 6.21 mmol) in the given order. The mixture was stirred for 2 h at room temperature, diluted with an aqueous solution of NaHCO3 (saturated, 25 mL) and then extracted three times with ethyl acetate. The combined organic solutions were washed three times with water and then dried over Na2SO4. The solvent was removed by evaporation and the residue was chromatographed on silica gel using a mixture of heptane and ethyl acetate as eluent (4:1). There was obtained 576 mg (85%) of N-[(2S)-2-(4-fluorophenyl)pent-4-en-1-yl]-N-methyl-3,5-bis(trifluoromethyl)benzamide as an oil. 1H NMR (400 MHz, CDCl3): 2.2-2.4 (cm, 2H), 2.7 (s, 2H), 2.9-3.9 (cm, 4H), 4.9-5.1 (m, 2H), 5.4-5.8 (m, 1H), 6.8-7.1 (cm, 3H), 7.2-7.5 (3H), 7.9 (s, 1H); LCMS: m/z 434 (M+1)+.

Workup

  1. extractionextracted three times with ethyl acetate
  2. washThe combined organic solutions were washed three times with water
  3. dry with materialdried over Na2SO4
  4. customThe solvent was removed by evaporation
  5. customthe residue was chromatographed on silica gel using
  6. additiona mixture of heptane and ethyl acetate as eluent (4:1)

Sources & evidence

ORD record
ord-1ca5c39587f34adabaff1b6f5c26df96
Source dataset
uspto-grants-2008_07
Patent number
US07402581B2

Reaction notes

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