Cesium carbonate → 5-Ethenyl-2-fluoro-pyridine

HRID 1621445Notes

Reaction equation

HRID 1621445 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([F:8])=[N:6][CH:7]=1.[CH:9]([B-](F)(F)F)=[CH2:10].[K+].C(=O)([O-])[O-].[Cs+].[Cs+]>C1COCC1.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:8][C:5]1[CH:4]=[CH:3][C:2]([CH:9]=[CH2:10])=[CH:7][N:6]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 27831685-Bromo-2-fluoropyridineHCID 23679353Potassium vinyltrifluoroborate

Product 1

HCID 574168425-Ethenyl-2-fluoro-pyridine

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
85 °C

Procedure

5-Bromo-2-fluoropyridine (Aldrich 99%, 5.14 g, 29.2 mmol) and potassium vinyltrifluoroborate (Aldrich, St. Louis, Mo., 4.23 g, 31.6 mmol) were suspended in THF (80 mL) and water (9.0 mL) and dichlorobis(triphenyl-phosphine)palladium (II) (0.627 g, 0.893 mmol) and cesium carbonate (28.5 g, 87.6 mmol) were added. The reaction flask was fitted with a reflux condenser and placed in a preheated oil bath (85° C.) and stirred overnight under nitrogen. Then, the reaction was cooled to room temperature and diluted with water (125 mL). The layers were separated, and the aqueous phase was extracted with DCM. The organic extracts were combined, dried over sodium sulfate, filtered, and concentrated (using an unheated water bath and a rotary evaporator pressure of 43-70 torr). The crude material was purified on a silica gel filter (about 3 inches) with DCM, and the fractions with product were collected, concentrated, and dried briefly under high vacuum. The material was triturated with Et2O and filtered, and the solid was washed with Et2O. The filtrate was concentrated and dried on two separate occasions on the high vacuum for about 10 seconds each to afford 2-fluoro-5-vinylpyridine, which was taken to the next step.

Workup

  1. customThe reaction flask was fitted with a reflux condenser
  2. customplaced in a preheated oil bath
  3. temperatureThen, the reaction was cooled to room temperature
  4. customThe layers were separated
  5. extractionthe aqueous phase was extracted with DCM
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated (
  9. customa rotary evaporator pressure of 43-70 torr)
  10. customThe crude material was purified on a silica gel
  11. filtrationfilter (about 3 inches) with DCM
  12. customthe fractions with product were collected
  13. concentrationconcentrated
  14. customdried briefly under high vacuum
  15. customThe material was triturated with Et2O
  16. filtrationfiltered
  17. washthe solid was washed with Et2O
  18. concentrationThe filtrate was concentrated
  19. customdried on two
  20. customseparate occasions on the high vacuum for about 10 seconds

Sources & evidence

ORD record
ord-cee6472e53de4844a0a59f26cf3932bd
Source dataset
uspto-grants-2014_07
Patent number
US08772480B2

Reaction notes

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