Water → (E)-3,3,3-Trifluoro-N-(5-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-2,3-dihydro-1H-inden-1-yl)propanamide

HRID 1503694Notes

Reaction equation

HRID 1503694 reaction equation
[F:1][C:2]([F:26])([F:25])[CH:3]([C:16]1[CH:21]=[C:20]([Cl:22])[C:19]([Cl:23])=[C:18]([Cl:24])[CH:17]=1)/[CH:4]=[CH:5]/[C:6]1[CH:7]=[C:8]2[C:12](=[CH:13][CH:14]=1)[CH:11]([NH2:15])[CH2:10][CH2:9]2.[F:27][C:28]([F:34])([F:33])[CH2:29][C:30](O)=[O:31].CCN=C=NCCCN(C)C.Cl.C1C=CC2N(O)N=NC=2C=1.O.CCN(C(C)C)C(C)C>C(Cl)Cl>[F:27][C:28]([F:34])([F:33])[CH2:29][C:30]([NH:15][CH:11]1[C:12]2[C:8](=[CH:7][C:6](/[CH:5]=[CH:4]/[CH:3]([C:16]3[CH:17]=[C:18]([Cl:24])[C:19]([Cl:23])=[C:20]([Cl:22])[CH:21]=3)[C:2]([F:1])([F:25])[F:26])=[CH:14][CH:13]=2)[CH2:9][CH2:10]1)=[O:31]

Participants

8

Reactant 6

HCID 962WaterHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27779723,3,3-Trifluoropropionic acidHCID 86675158(E)-5-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-2,3-dihydro-1H-inden-1-amine

Product 1

HCID 89306424(E)-3,3,3-Trifluoro-N-(5-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-2,3-dihydro-1H-inden-1-yl)propanamideYield 65%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a stirred solution of (E)-5-(4,4,4-trifluoro-3-(3,4,5-trichlorophenyl)but-1-enyl)-2,3-dihydro-1H-inden-1-amine (0.1 g, 0.23 mmol) in CH2Cl2 (10 mL) were added trifluoropropionic acid (0.044 g, 0.34 mmol), EDC.HCl (0.038 g, 0.35 mmol), HOBt.H2O (0.07 g, 0.46 mmol) and DIEA (0.074 g, 0.57 mmol), and the reaction mixture was stirred for 16 h at 25° C. The reaction mixture was diluted with CH2Cl2 and washed with H2O. The combined organic layer was washed with brine, dried over anhydrous Na2SO4, and concentrated under reduced pressure. The crude material was purified by flash column chromatography (SiO2, 15% EtOAc in petroleum ether) to afford the title compound as a liquid (65 mg, 65%): 1H NMR (400 MHz, CDCl3) δ 7.39 (s, 2H), 7.25-7.20 (m, 3H), 6.34 (d, J=16.0 Hz, 1H), 6.30 (dd, J=16.0, 8.0 Hz, 1H), 5.81 (br, 1H), 5.48 (m, 1H), 4.10 (m, 1H), 3.10 (m, 2H), 2.86-3.07 (m, 2H), 2.86 (m, 1H), 1.81 (m, 1H); ESIMS m/z 529.02 ([M+H]+); IR (thin film) 3283, 1652, 1241, 811 cm−1.

Workup

  1. washwashed with H2O
  2. washThe combined organic layer was washed with brine
  3. dry with materialdried over anhydrous Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customThe crude material was purified by flash column chromatography (SiO2, 15% EtOAc in petroleum ether)

Sources & evidence

ORD record
ord-f23a2d9bff7146768461c1ef6ca18e36
Source dataset
uspto-grants-2015_12
Patent number
US09212164B2

Reaction notes

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