3,5-Dibromopyridine → HCID 17975614, compound

HRID 1765107Notes

Reaction equation

HRID 1765107 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Br:8])[CH:7]=1.[F:9][C:10]1[CH:11]=[CH:12][C:13](B2OC(C)(C)C(C)(C)O2)=[C:14]([CH:17]=1)[C:15]#[N:16]>COCCOC.C(=O)([O-])[O-].[Na+].[Na+].O>[Br:8][C:6]1[CH:7]=[C:2]([C:13]2[CH:12]=[CH:11][C:10]([F:9])=[CH:17][C:14]=2[C:15]#[N:16])[CH:3]=[N:4][CH:5]=1

Participants

6

Reactant 2

HCID 693693,5-DibromopyridineHCID 221807905-Fluoro-2-(tetramethyl-1,3,2-dioxaborolan-2-yl)benzonitrile

Product 1

HCID 17975614HCID 17975614, compoundYield 90.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolventHCID 10340Sodium CarbonateSolvent

Procedure

A solution of 3,5-dibromopyridine (1.0 g, 4.2 mmol) and 5-fluoro-2-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)benzonitrile (0.95 g, 3.8 mmol) in 1,2-dimethoxyethane (20 ml) and 2N sodium carbonate solution (10 ml) was degassed with nitrogen for 30 min. Tetrakis-(triphenylphosphine)palladium(0) (89 mg, 0.08 mmol) was added and the mixture heated under reflux for 18 h. The mixture was allowed to cool to ambient temperature, diluted with water (10 ml) then extracted with ethyl acetate (2×100 ml). The organics were combined, dissolved in phophorus oxychloride (50 ml) and heated at 100° C. for 2 h. The reaction mixture was allowed to cool to ambient temperature and concentrated. The residue was treated with ice, and the resulting solution was layered with ethyl acetate (30 ml) and made basic by the addition of solid sodium hydrogencarbonate. The layers were separated, and the aqueous extracted further with ethyl acetate (75 ml). The organics were combined, washed with brine (20 ml), dried over anhydrous magnesium sulfate, filtered and evaporated to give a colourless oil. The oil was purified by flash column chromatography on silica, eluting with isohexane on a gradient of ethyl acetate (20-50%), to give 2-(5-bromopyridin-3-yl)-5-fluorobenzonitrile (0.95 g, 81%) as a white solid: δH (360 MHz, CDCl3) 7.44-7.46 (1H, m), 7.49-7.54 (2H, m), 8.02 (1H, s), 8.67 (1H, d, J 1.8), 8.78 (1H, d, J 1.8).

Workup

  1. temperaturethe mixture heated
  2. temperatureunder reflux for 18 h
  3. extractionthen extracted with ethyl acetate (2×100 ml)
  4. dissolutiondissolved in phophorus oxychloride (50 ml)
  5. temperatureheated at 100° C. for 2 h
  6. temperatureto cool to ambient temperature
  7. concentrationconcentrated
  8. additionThe residue was treated with ice
  9. additionmade basic by the addition of solid sodium hydrogencarbonate
  10. customThe layers were separated
  11. extractionthe aqueous extracted further with ethyl acetate (75 ml)
  12. washwashed with brine (20 ml)
  13. dry with materialdried over anhydrous magnesium sulfate
  14. filtrationfiltered
  15. customevaporated
  16. customto give a colourless oil
  17. customThe oil was purified by flash column chromatography on silica
  18. washeluting with isohexane on a gradient of ethyl acetate (20-50%)

Sources & evidence

ORD record
ord-4a29cc63e4c5441e8468f8f3f890e790
Source dataset
uspto-grants-2007_06
Patent number
US07226926B2

Reaction notes

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