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 1502975Notes

Reaction equation

HRID 1502975 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 DIPEA (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 water. 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 water
  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-f3c4b6fc490042aa8c0a84457113067a
Source dataset
uspto-grants-2015_12
Patent number
US09211281B2

Reaction notes

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