2,2,2-Trifluoroethanol → 3-Bromo-5-(2,2,2-trifluoroethoxy)pyridine

HRID 24050Notes

Reaction equation

HRID 24050 reaction equation
[H-].[Na+].[F:3][C:4]([F:8])([F:7])[CH2:5][OH:6].[Br:9][C:10]1[CH:11]=[N:12][CH:13]=[C:14](Br)[CH:15]=1>CN(C=O)C.O>[Br:9][C:10]1[CH:11]=[N:12][CH:13]=[C:14]([O:6][CH2:5][C:4]([F:8])([F:7])[F:3])[CH:15]=1

Participants

6

Reactant 3

HCID 64092,2,2-TrifluoroethanolHCID 24758Sodium hydrideHCID 693693,5-Dibromopyridine

Product 1

HCID 225703523-Bromo-5-(2,2,2-trifluoroethoxy)pyridineYield 46%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent2×

Conditions

Temperature
70 °C

Procedure

To a slurry of sodium hydride (60% dispersion in mineral oil, 0.54 g, 14 mmol) in DMF (15 mL) was added commercially available 2,2,2-trifluoroethanol (0.97 mL, 14 mmol) at room temperature. After stirring for 15 minutes, a solution of 3,5-dibromopyridine (3.2 g, 14 mmol) in 5 mL of DMF was added dropwise. The reaction mixture was heated overnight at 70° C. After cooling to room temperature, the reaction was diluted with water and extracted with ethyl acetate. The extracts were dried over magnesium sulfate and the solvent was removed under reduced pressure. The crude product was chromatographed on silica (5% ethyl acetate/hexanes) to give the title compound (1.6 g, 46% yield) as clear oil. 1H NMR (CDCl3) δ 8.42 (d, 1H, J=1.7 Hz), 8.32 (d, 1H, J=2.5 Hz), 7.46 (m, 1H), 4.42 (m, 2H).

Workup

  1. temperatureAfter cooling to room temperature
  2. extractionextracted with ethyl acetate
  3. dry with materialThe extracts were dried over magnesium sulfate
  4. customthe solvent was removed under reduced pressure
  5. customThe crude product was chromatographed on silica (5% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-846bceea113f4a91acc8e987af3cd9ec
Source dataset
uspto-grants-2005_02
Patent number
US06855722B2

Reaction notes

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