4-Chloroaniline → 3-(4-Bromo-2-fluoro-phenyl)-N-(4-chloro-phenyl)-acrylamide

HRID 1011652Notes

Reaction equation

HRID 1011652 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]=[CH:9][C:10]([OH:12])=O)=[C:4]([F:13])[CH:3]=1.[Cl:14][C:15]1[CH:21]=[CH:20][C:18]([NH2:19])=[CH:17][CH:16]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C>ClCCl>[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]=[CH:9][C:10]([NH:19][C:18]2[CH:20]=[CH:21][C:15]([Cl:14])=[CH:16][CH:17]=2)=[O:12])=[C:4]([F:13])[CH:3]=1

Participants

6

Reactant 4

HCID 78124-ChloroanilineHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 6883133-(4-Bromo-2-fluorophenyl)-2-propenoic acid

Product 1

HCID 673138123-(4-Bromo-2-fluoro-phenyl)-N-(4-chloro-phenyl)-acrylamideYield 82%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 3-(4-bromo-2-fluoro-phenyl)-acrylic acid (12.7 g, 52 mmol), 4-chloroaniline (9.9 g, 78 mmol), HOBt (10.5 g, 78 mmol) and EDCI (15.0 g, 78 mmol) in 200 mL of dichloromethane was refluxed overnight, and the resulting mixture was washed with 1M NaOH solution, water and brine, dried over Na2SO4, and concentrated. Recrystallization of the residue from EtOAc/Hexane gave 15 g (82%) of white solid. MS: calc'd 354 (MH+), exp 354 (MH+). 1H NMR (CDCl3, 400 MHz), 7.75 (d, 1H, J=15.6 Hz), 7.60 (d, 2H, J=8.8 Hz), 7.48 (s, 1H), 7.32-7.38 (m, 5H, J=7.6 Hz), 6.70 (d, 1H, J=15.6 Hz).

Workup

  1. temperaturewas refluxed overnight
  2. washthe resulting mixture was washed with 1M NaOH solution, water and brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated
  5. customRecrystallization of the residue from EtOAc/Hexane

Sources & evidence

ORD record
ord-120a4ce3b7964066a59fbc6c1de79da2
Source dataset
uspto-grants-2011_07
Patent number
US07977372B2

Reaction notes

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