2,2'-Bipyridine → (E)-2-Amino-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-N-(2-oxo-2-(2,2,2-trifluoroethylamino)ethyl)benzamide

HRID 587784Notes

Reaction equation

HRID 587784 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:10]([C:27]([F:30])([F:29])[F:28])/[CH:11]=[CH:12]/[C:13]2[CH:23]=[CH:22][C:16]([C:17](OCC)=[O:18])=[C:15]([N+:24]([O-])=O)[CH:14]=2)[CH:5]=[C:6]([Cl:9])[C:7]=1[F:8].Br[CH:32](C1C=C(Cl)C(F)=C(Cl)C=1)[C:33]([F:36])([F:35])[F:34].[N:46]1C=CC=C[C:47]=1[C:52]1C=CC=C[N:53]=1.[N+](C1C=C(C=C)C=CC=1C(OCC)=O)([O-])=[O:59]>ClC1C=CC=CC=1Cl.Cl[Cu]>[NH2:24][C:15]1[CH:14]=[C:13](/[CH:12]=[CH:11]/[CH:10]([C:4]2[CH:3]=[C:2]([Cl:1])[C:7]([F:8])=[C:6]([Cl:9])[CH:5]=2)[C:27]([F:28])([F:29])[F:30])[CH:23]=[CH:22][C:16]=1[C:17]([NH:46][CH2:47][C:52](=[O:59])[NH:53][CH2:32][C:33]([F:34])([F:35])[F:36])=[O:18]

Participants

7

Reactant 4

HCID 14742,2'-BipyridineHCID 866751625-(1-Bromo-2,2,2-trifluoroethyl)-1,3-dichloro-2-fluorobenzeneHCID 86722761(E)-Ethyl 4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-2-nitrobenzoateHCID 86722762Ethyl 2-nitro-4-vinylbenzoate

Product 1

HCID 86722765(E)-2-Amino-4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-N-(2-oxo-2-(2,2,2-trifluoroethylamino)ethyl)benzamideYield 53%

Reagents, catalysts & solvents 2

HCID 62652Cuprous chlorideCatalystHCID 72391,2-DichlorobenzeneSolvent

Conditions

Temperature
180 °C

Procedure

(E)-Ethyl 4-(3-(3,5-dichloro-4-fluorophenyl)-4,4,4-trifluorobut-1-enyl)-2-nitrobenzoate: 5-(1-Bromo-2,2,2-trifluoroethyl)-1,3-dichloro-2-fluorobenzene (3.5 g, 10.8 mmol), CuCl (54 mg, 0.54 mmol) and 2,2-bipyridyl (169 mg, 1.08 mmol) were added to a stirred solution of ethyl 2-nitro-4-vinylbenzoate (1.2 g, 5.42 mmol) in 1,2-dichlorobenzene (12 mL) at ambient temperature and the mixture was then stirred at 180° C. for 18 h. The reaction mixture was then cooled to ambient temperature, adsorbed on silica gel and purified by column chromatography eluting with 10% EtOAc in petroleum ether to afford the title compound (1.3 g, 53%) as a brown liquid: 1H NMR (DMSO-d6, 300 MHz) δ 8.31 (s, 1H), 8.02-7.95 (m, 1H), 7.88-7.85 (m, 3H), 7.20 (dd, J=15.9, 9.3 Hz, 1H), 6.91 (d, J=15.6 Hz, 1H), 4.91-4.85 (m, 1H), 4.34-4.27 (m, 2H), 1.27 (t, J=6.6 Hz, 3H); ESIMS m/z 463.8 ([M−H]−); IR (KBr) 3439, 2985, 1731, 1251 cm−1.

Workup

  1. temperatureThe reaction mixture was then cooled to ambient temperature
  2. custompurified by column chromatography
  3. washeluting with 10% EtOAc in petroleum ether

Sources & evidence

ORD record
ord-1c34f66e58ac4833927c4b0919f687c6
Source dataset
uspto-grants-2016_01
Patent number
US09226501B2

Reaction notes

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