Dimethylformamide → 5-Bromo-2-(2,2,2-trifluoroethoxy)pyridine

HRID 1630736Notes

Reaction equation

HRID 1630736 reaction equation
[F:1][C:2]([F:6])([F:5])[CH2:3][OH:4].CN(C=O)C.[H-].[Na+].Br[C:15]1[CH:20]=[CH:19][C:18]([Br:21])=[CH:17][N:16]=1>CCOC(C)=O>[Br:21][C:18]1[CH:19]=[CH:20][C:15]([O:4][CH2:3][C:2]([F:6])([F:5])[F:1])=[N:16][CH:17]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 64092,2,2-TrifluoroethanolHCID 24758Sodium hydrideHCID 693532,5-Dibromopyridine

Product 1

HCID 223919645-Bromo-2-(2,2,2-trifluoroethoxy)pyridine

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
25 °C

Procedure

2,2,2-Trifluoroethanol (6.15 mL, 84.4 mmol) was placed into a flask with DMF (141 mL). To the reaction mixture was added NaH (3.4 g, 84.4 mmol) in portions. The reaction was then stirred for 30 min at 25° C. At this point, 2,5-dibromopyridine was added and the mixture was heated to 90° C. and stirred at that temperature overnight. The reaction was cooled to rt and diluted with EtOAc (100 mL). The organic layer was washed with H2O (3×150 mL), brine (2×100 mL), dried (MgSO4), filtered, and concentrated. This material was purified by column chromatography (15:1 hexane:EtOAc) to give 5-bromo-2-(2,2,2-trifluoroethoxy)pyridine as an oil.

Workup

  1. temperaturethe mixture was heated to 90° C.
  2. stirringstirred at that temperature overnight
  3. temperatureThe reaction was cooled to rt
  4. washThe organic layer was washed with H2O (3×150 mL), brine (2×100 mL)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThis material was purified by column chromatography (15:1 hexane:EtOAc)

Sources & evidence

ORD record
ord-abcff1384a424f25a100900249987557
Source dataset
uspto-grants-2014_07
Patent number
US08791147B2

Reaction notes

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