Homoveratrylamine → N-[2-(3,4-Dimethoxyphenyl)ethyl]-3-[4-(trifluoromethyl)phenyl]propanamide

HRID 660021Notes

Reaction equation

HRID 660021 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][C:11]=1[O:12][CH3:13])[CH2:6][CH2:7][NH2:8].[F:14][C:15]([F:28])([F:27])[C:16]1[CH:26]=[CH:25][C:19]([CH2:20][CH2:21][C:22](O)=[O:23])=[CH:18][CH:17]=1>C1(C)C=CC=CC=1.C(OCC)(=O)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:9]=[CH:10][C:11]=1[O:12][CH3:13])[CH2:6][CH2:7][NH:8][C:22](=[O:23])[CH2:21][CH2:20][C:19]1[CH:18]=[CH:17][C:16]([C:15]([F:27])([F:28])[F:14])=[CH:26][CH:25]=1

Participants

5

Reactant 2

HCID 8421HomoveratrylamineHCID 35887363-(4-(Trifluoromethyl)phenyl)propionic Acid

Product 1

HCID 27282117N-[2-(3,4-Dimethoxyphenyl)ethyl]-3-[4-(trifluoromethyl)phenyl]propanamideYield 70.4%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

3,4-Dimethoxyphenethylamine 42a (3.62 g, 3.4 mL, 20 mmol, 1.0 eq) was added to a solution of 4-(trifluoromethyl)hydrocinnamic acid 43 (4.36 g, 20 mmol, 1.0 eq) in toluene (75 mL). After 5 min a thick suspension formed. The suspension was heated to reflux, giving a clear solution. The mixture was heated at reflux for 24 h using a Dean-Stark trap to remove water that was formed. The mixture was partially cooled, diluted with ethyl acetate (100 mL) and concentrated under reduced pressure to near dryness. The thick slurry was diluted with ethyl acetate (200 mL) and the solution washed sequentially with 1N hydrochloric acid (100 mL), aqueous sodium bicarbonate solution (200 mL), water (100 mL) and brine (100 mL). The organic solution was dried over sodium sulfate, filtered and the filtrate concentrated under reduced pressure. The solid was triturated with heptanes (50 mL), filtered and dried to give 5.37 g (70%) of 44a as a white, fluffy solid.

Workup

  1. customAfter 5 min a thick suspension formed
  2. temperatureThe suspension was heated
  3. temperatureto reflux
  4. customgiving a clear solution
  5. temperatureThe mixture was heated
  6. temperatureat reflux for 24 h
  7. customto remove water that
  8. customwas formed
  9. temperatureThe mixture was partially cooled
  10. concentrationconcentrated under reduced pressure
  11. additionThe thick slurry was diluted with ethyl acetate (200 mL)
  12. washthe solution washed sequentially with 1N hydrochloric acid (100 mL), aqueous sodium bicarbonate solution (200 mL), water (100 mL) and brine (100 mL)
  13. dry with materialThe organic solution was dried over sodium sulfate
  14. filtrationfiltered
  15. concentrationthe filtrate concentrated under reduced pressure
  16. customThe solid was triturated with heptanes (50 mL)
  17. filtrationfiltered
  18. customdried

Sources & evidence

ORD record
ord-e6de97f2c18247b7a2ab6aaebc9a3186
Source dataset
uspto-grants-2011_12
Patent number
US08084464B2

Reaction notes

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