Ethanamine, 2,2,2-trifluoro- → (E)-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-enyl)-2-methyl-N-(2,2,2-trifluoroethyl)benzamide

HRID 587669Notes

Reaction equation

HRID 587669 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]([C:22]([F:25])([F:24])[F:23])/[CH:10]=[CH:11]/[C:12]2[CH:20]=[CH:19][C:15]([C:16]([OH:18])=O)=[C:14]([CH3:21])[CH:13]=2)[CH:5]=[C:6]([Cl:8])[CH:7]=1.[F:26][C:27]([F:31])([F:30])[CH2:28][NH2:29].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.CCN(C(C)C)C(C)C>CN(C=O)C.O>[Cl:8][C:6]1[CH:5]=[C:4]([CH:9]([C:22]([F:25])([F:24])[F:23])/[CH:10]=[CH:11]/[C:12]2[CH:20]=[CH:19][C:15]([C:16]([NH:29][CH2:28][C:27]([F:31])([F:30])[F:26])=[O:18])=[C:14]([CH3:21])[CH:13]=2)[CH:3]=[C:2]([Cl:1])[CH:7]=1

Participants

8

Reactant 5

HCID 9773Ethanamine, 2,2,2-trifluoro-HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 86675124(E)-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-enyl)-2-methylbenzoic acid

Product 1

HCID 86675125(E)-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-enyl)-2-methyl-N-(2,2,2-trifluoroethyl)benzamideYield 50%

Reagents, catalysts & solvents 2

HCID 962WaterSolvent2×HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of (E)-4-(3-(3,5-dichlorophenyl)-4,4,4-trifluorobut-1-enyl)-2-methylbenzoic acid in DMF was added 2,2,2-trifluoroethylamine, HOBt.H2O, EDC.HCl and DIPEA, and the reaction mixture was stirred at 25° C. for 18 h. The reaction mixture was diluted with water and extracted with EtOAc. The combined organic layer was washed with brine, dried over Na2SO4 and concentrated under reduced pressure. Purification by flash column chromatography (SiO2, 100-200 mesh; eluting with hexane:EtOAc afforded a white semi-solid (110 mg, 50%): 1H NMR (400 MHz, CDCl3) 7.40 (m, 2H), 7.26 (m, 3H), 6.56 (d, J=16.0 Hz, 1H), 6.48 (dd, J=16.0, 8.0 Hz, 1H), 5.82 (br s, 1H), 4.08 (m, 3H), 2.52 (s, 3H); ESIMS m/z 468.40 ([M−H]−); IR (thin film) 1657, 1113, 804 cm−1.

Workup

  1. extractionextracted with EtOAc
  2. washThe combined organic layer was washed with brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customPurification by flash column chromatography (SiO2, 100-200 mesh
  6. washeluting with hexane

Sources & evidence

ORD record
ord-fa581db0b7834451901f01aa6ea5d043
Source dataset
uspto-grants-2016_01
Patent number
US09226501B2

Reaction notes

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