Pyridine → N-(2,4-difluorophenyl)cinnamamide

HRID 2035631Notes

Reaction equation

HRID 2035631 reaction equation
[F:1][C:2]1[CH:8]=[C:7]([F:9])[CH:6]=[CH:5][C:3]=1[NH2:4].N1C=CC=CC=1.[C:16](Cl)(=[O:25])[CH:17]=[CH:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>ClCCl>[F:1][C:2]1[CH:8]=[C:7]([F:9])[CH:6]=[CH:5][C:3]=1[NH:4][C:16](=[O:25])[CH:17]=[CH:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 97092,4-DifluoroanilineHCID 660233-Phenylprop-2-enoyl chloride

Product 1

HCID 755462N-(2,4-difluorophenyl)cinnamamideYield 74.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Conditions

Temperature
0 °C

Procedure

2,4-difluoroaniline (9.0 g, 69.71 mmol) and pyridine (5.6 mL, 69.71 mmol) were dissolved in dichloromethane (45 mL) and the solution was cooled to 0° C. A solution of cinnamoyl chloride (13.04 g, 76.7 mmol) dissolved in dichloromethane (45 mL) was added dropwise, and after the addition the reaction was warmed to ambient temperature and stirred for 16 hours. The reaction was quenched with saturated NaHCO3 and the layers were separated. The organic layer was washed with 1 M HCl then dried over Na2SO4 and concentrated in vacuo to provide a white solid. The solid was slurried in dichloromethane (150 mL), stirred for 30 minutes, and then hexanes (150 mL) were added. After stirring several minutes, the white solids were collected by filtration, washed with dichloromethane and air-dried to provide 13.5 g of the desired product. MS APCI (−) m/z 258.0 (M−1) detected.

Workup

  1. additionwas added dropwise
  2. additionafter the addition the reaction
  3. temperaturewas warmed to ambient temperature
  4. customThe reaction was quenched with saturated NaHCO3
  5. customthe layers were separated
  6. washThe organic layer was washed with 1 M HCl
  7. dry with materialthen dried over Na2SO4
  8. concentrationconcentrated in vacuo
  9. customto provide a white solid
  10. stirringstirred for 30 minutes
  11. stirringAfter stirring several minutes
  12. filtrationthe white solids were collected by filtration
  13. washwashed with dichloromethane
  14. customair-dried

Sources & evidence

ORD record
ord-0caaa8d9c98f4f8aa22835ed3f863905
Source dataset
uspto-grants-2013_11
Patent number
US08575145B2

Reaction notes

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