Sodium Carbonate → (E)-5-Bromo-3-(2,5-difluorostyryl)-2-fluoropyridine

HRID 2362413Notes

Reaction equation

HRID 2362413 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[CH:9]=[CH2:10].[Br:11][C:12]1[CH:13]=[C:14](B2OC(C)(C)C(C)(C)O2)[C:15]([F:18])=[N:16][CH:17]=1.C(=O)([O-])[O-].[Na+].[Na+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CN(C=O)C>[Br:11][C:12]1[CH:13]=[C:14](/[CH:10]=[CH:9]/[C:3]2[CH:4]=[C:5]([F:8])[CH:6]=[CH:7][C:2]=2[F:1])[C:15]([F:18])=[N:16][CH:17]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 218718902,5-DifluorostyreneHCID 447551895-Bromo-2-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine

Product 1

HCID 69084839(E)-5-Bromo-3-(2,5-difluorostyryl)-2-fluoropyridine

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Procedure

A round bottom flask was charged with 1,4-difluoro-2-vinylbenzene (1 g, 7.14 mmol), 5-bromo-2-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (2.69 g, 8.92 mmol), and DMF (27 mL). The resulting mixture was purged with a stream of oxygen for 10 min. To this was added sodium carbonate (1.89 g, 17.8 mmol) and palladium (II) acetate (0.128 g, 0.571 mmol) as a solid in a single portion. The reaction was purged with oxygen for 5 min. The reaction was fitted with a balloon of oxygen and stirred at room temperature overnight. In the morning, the reaction was diluted with ethyl acetate and poured into water. The mixture was treated with excess celite and filtered to remove solids. The organic layer was washed with water (2×), then brine, dried over magnesium sulfate, and concentrated. Column chromatography (10% EtOAc/Hex) gave 409 mg (17%). 1H NMR (CDCl3) δ: 8.16-8.22 (m, 1H), 8.13 (dd, J=8.2, 2.4 Hz, 1H), 7.29-7.39 (m, 2H), 7.06-7.20 (m, 2H), 6.97-7.06 (m, 1H). 19F NMR (CDCl3) δ: −74.07 (d, J=8.7 Hz, 1F), −118.78 (d, J=8.7 Hz, 1F), −123.39 (br. s., 1F). Mass spec.: 314.1 (MH)+.

Workup

  1. customThe resulting mixture was purged with a stream of oxygen for 10 min
  2. customThe reaction was purged with oxygen for 5 min
  3. customThe reaction was fitted with a balloon of oxygen
  4. additionIn the morning, the reaction was diluted with ethyl acetate
  5. additionpoured into water
  6. additionThe mixture was treated with excess celite and
  7. filtrationfiltered
  8. customto remove solids
  9. washThe organic layer was washed with water (2×)
  10. dry with materialbrine, dried over magnesium sulfate
  11. concentrationconcentrated
  12. customColumn chromatography (10% EtOAc/Hex) gave 409 mg (17%)

Sources & evidence

ORD record
ord-a1007c6015354dc79c029728f4009484
Source dataset
uspto-grants-2014_04
Patent number
US08691821B2

Reaction notes

Loading…