Ethyl Acetate → 2-Fluoro-N,N-dimethyl-4-(pyridin-4-yl)aniline

HRID 240226Notes

Reaction equation

HRID 240226 reaction equation
Br[C:2]1[CH:10]=[CH:9][C:5]([N:6]([CH3:8])[CH3:7])=[C:4]([F:11])[CH:3]=1.C(B(CC)[C:15]1[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=1)C.[OH-].[K+].C(OCC)(=O)C>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.O1CCCC1.[Cl-].[Na+].O>[F:11][C:4]1[CH:3]=[C:2]([C:15]2[CH:20]=[CH:19][N:18]=[CH:17][CH:16]=2)[CH:10]=[CH:9][C:5]=1[N:6]([CH3:8])[CH3:7]

Participants

8

Reactant 4

HCID 8857Ethyl AcetateHCID 14797Potassium HydroxideHCID 133188714-(Diethylboranyl)pyridineHCID 404253644-bromo-2-fluoro-N,N-dimethylaniline

Product 1

HCID 672021852-Fluoro-N,N-dimethyl-4-(pyridin-4-yl)anilineYield 46.2%

Reagents, catalysts & solvents 3

HCID 74236Tetrabutylammonium BromideCatalystHCID 8028TetrahydrofuranSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

4-Bromo-2-fluoro-N,N-dimethyl aniline (2.83 g, 13 mmols), tetrakis triphenyl palladium (0) (0.508 g, 0.4 mmols), diethyl (4-pyridyl borane) (1.3 g, 9 mmols), potassium hydroxide (2.81 g, 50 mmols) and tetrabutylammonium bromide (1.42 g, 4 mmols) were combined in tetrahydrofuran (50 ml). The resulting mixture was heated at reflux for 18 hrs under nitrogen then cooled to ambient temperature. Ethyl acetate (100 ml) and brine (50 ml) were added and the organic solution was separated. This was dried over magnesium sulfate filtered and evaporated to yield a yellow solid. The product was purified by column chromatography on silica eluted with ethyl acetate:hexanes 50:50 to give 0.9 g of 2-Fluoro-N,N-dimethyl-4-(pyridin-4-yl)aniline (XII) in a 44% yield as a pale yellow solid.

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureat reflux for 18 hrs under nitrogen
  3. customthe organic solution was separated
  4. dry with materialThis was dried over magnesium sulfate
  5. filtrationfiltered
  6. customevaporated
  7. customto yield a yellow solid
  8. customThe product was purified by column chromatography on silica
  9. washeluted with ethyl acetate:hexanes 50:50

Sources & evidence

ORD record
ord-679ebbcbb9de42268d302d621ffbe7de
Source dataset
uspto-grants-2014_02
Patent number
US08647827B2

Reaction notes

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