2-Chloro-3-methyl-5-nitropyridine → 3-Methyl-5-nitro-2-[4-(trifluoromethyl)phenyl]pyridine

HRID 1160872Notes

Reaction equation

HRID 1160872 reaction equation
Cl[C:2]1[C:7]([CH3:8])=[CH:6][C:5]([N+:9]([O-:11])=[O:10])=[CH:4][N:3]=1.[F:12][C:13]([F:24])([F:23])[C:14]1[CH:19]=[CH:18][C:17](B(O)O)=[CH:16][CH:15]=1.[F-].[K+]>C1(C)C=CC=CC=1>[CH3:8][C:7]1[C:2]([C:17]2[CH:18]=[CH:19][C:14]([C:13]([F:24])([F:23])[F:12])=[CH:15][CH:16]=2)=[N:3][CH:4]=[C:5]([N+:9]([O-:11])=[O:10])[CH:6]=1

Participants

5

Reactant 3

HCID 896482-Chloro-3-methyl-5-nitropyridineHCID 522689Potassium FluorideHCID 27343894-(Trifluoromethyl)phenylboronic acid

Product 1

HCID 671534333-Methyl-5-nitro-2-[4-(trifluoromethyl)phenyl]pyridine

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a solution of 2-chloro-3-methyl-5-nitro-pyridine (5.0 g, 28.73 mmol) in toluene (50 mL) is added palladium tetrakis triphenylphosphine (1.66 g, 1.44 mmol), 4-trifluoromethyl phenyl boronic acid (10.92 g, 57.46 mmol), and potassium fluoride (3.34 g, 57.46 mmol). The reaction is purged with nitrogen three times and heated to reflux under nitrogen. At reflux, water (25 mL) is added to the reaction and the reaction is allowed to reflux under nitrogen. The reaction is monitored by HPLC, and upon completion, allowed to cool to room temperature. The reaction is diluted with ethyl acetate and Celite is added, followed by water. This mixture is then filtered through a pad of Celite. The solution is poured into a separatory funnel and the organic layer is washed with water and brine. The organic layer is dried over anhydrous sodium sulfate and concentrated. The product is purified by flash column chromatography (5.6 g, 19.71 mmol).

Workup

  1. customThe reaction is purged with nitrogen three times
  2. temperatureheated
  3. temperatureto reflux under nitrogen
  4. temperatureAt reflux
  5. additionwater (25 mL) is added to the reaction
  6. temperatureto reflux under nitrogen
  7. additionThe reaction is diluted with ethyl acetate and Celite
  8. additionis added
  9. filtrationThis mixture is then filtered through a pad of Celite
  10. additionThe solution is poured into a separatory funnel
  11. washthe organic layer is washed with water and brine
  12. dry with materialThe organic layer is dried over anhydrous sodium sulfate
  13. concentrationconcentrated
  14. customThe product is purified by flash column chromatography (5.6 g, 19.71 mmol)

Sources & evidence

ORD record
ord-a48b75f2113c437a9e4cf0f9e287fca6
Source dataset
uspto-grants-2010_10
Patent number
US07816557B2

Reaction notes

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