Oxygen → (E)-5-Bromo-2-fluoro-3-(3-fluorostyryl)pyridine

HRID 2362361Notes

Reaction equation

HRID 2362361 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([CH:8]=[CH2:9])[CH:3]=1.[Br:10][C:11]1[CH:12]=[C:13](B(O)O)[C:14]([F:17])=[N:15][CH:16]=1.C(=O)([O-])[O-].[Na+].[Na+].O=O>CN(C)C=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Br:10][C:11]1[CH:12]=[C:13](/[CH:9]=[CH:8]/[C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([F:1])[CH:3]=2)[C:14]([F:17])=[N:15][CH:16]=1

Participants

7

Reactant 4

HCID 977OxygenHCID 10340Sodium CarbonateHCID 676913-FluorostyreneHCID 27832425-Bromo-2-fluoropyridine-3-boronic Acid (contains varying amounts of Anhydride)

Product 1

HCID 69082804(E)-5-Bromo-2-fluoro-3-(3-fluorostyryl)pyridine

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Procedure

To a 100 mL round bottom flask was added 1-fluoro-3-vinylbenzene (1.2 g, 9.82 mmol), 5-bromo-2-fluoropyridin-3-ylboronic acid (3.24 g, 14.74 mmol), and Sodium carbonate (2.60 g, 24.56 mmol) in dimethylformamide (32.7 ml). The reaction vessel was sealed and purged with oxygen via a balloon for 5 min. After purging with oxygen, palladium (II) acetate (0.221 g, 0.982 mmol) added and immediately purged with oxygen for (15 min.). The reaction was kept under a blanket of oxygen and left to stir overnight at room temperature. The reaction was then quenched with water and extracted with ethylacetate (3×). The organic layer was separated, washed with brine, dried over sodium sulfate, and concentrated in vacuo. The crude oil was loaded onto 90 g silica gel cartridge and the product was eluted with 5% DCM/Hex. The product fractions were collected and concentrated to afford 0.712 g (22%) as an off white crystalline solid. 1H-NMR (CDCl3, 400 MHz) δ 8.16 (s, 1H), 8.09 (dd, J=8.5, 2.3, 1H), 7.42-7.29 (m, 2H), 7.27-7.17 (m, 2H), 7.11-7.01 (m, 2H), LC/Mass spec. (Analytical HPLC method 2): RT=2.88 min. Mass=296.01 (MH)+.

Workup

  1. customThe reaction vessel was sealed
  2. custompurged with oxygen via a balloon for 5 min
  3. additionadded
  4. customimmediately purged with oxygen for (15 min.)
  5. waitleft
  6. customThe reaction was then quenched with water
  7. extractionextracted with ethylacetate (3×)
  8. customThe organic layer was separated
  9. washwashed with brine
  10. dry with materialdried over sodium sulfate
  11. concentrationconcentrated in vacuo
  12. washthe product was eluted with 5% DCM/Hex
  13. customThe product fractions were collected
  14. concentrationconcentrated
  15. customto afford 0.712 g (22%) as an off white crystalline solid

Sources & evidence

ORD record
ord-9966069bdbca44e78b0ad3c5ae5ff282
Source dataset
uspto-grants-2014_04
Patent number
US08691821B2

Reaction notes

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