Sodium Carbonate → (E)-2-bromo-5-fluoro-4-(4-fluorostyryl)pyridine

HRID 2362369Notes

Reaction equation

HRID 2362369 reaction equation
[Br:1][C:2]1[CH:7]=[C:6](B(O)O)[C:5]([F:11])=[CH:4][N:3]=1.C(=O)([O-])[O-].[Na+].[Na+].[F:18][C:19]1[CH:24]=[CH:23][C:22]([CH:25]=[CH2:26])=[CH:21][CH:20]=1>CN(C)C=O.C(O[Pd]OC(=O)C)(=O)C>[Br:1][C:2]1[CH:7]=[C:6](/[CH:26]=[CH:25]/[C:22]2[CH:23]=[CH:24][C:19]([F:18])=[CH:20][CH:21]=2)[C:5]([F:11])=[CH:4][N:3]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 678834-FluorostyreneHCID 44631046(2-Bromo-5-fluoropyridin-4-yl)boronic acid

Product 1

HCID 86673417(E)-2-bromo-5-fluoro-4-(4-fluorostyryl)pyridineYield 8.3%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 6228DimethylformamideSolvent

Procedure

To a 25 mL round bottom flask was added 2-bromo-5-fluoropyridin-4-ylboronic acid (1440 mg, 6.55 mmol), sodium carbonate (1085 mg, 10.23 mmol), and 1-fluoro-4-vinylbenzene (500 mg, 4.09 mmol) in dimethylformamide (8 mL). The solution was stirred at room temperature and the flask was purged with oxygen for 3 min. To the purged flask was quickly added diacetoxypalladium (92 mg, 0.409 mmol) and the reaction flask was again sealed and purged with oxygen for 15 min. The reaction mixture was then stirred at room temperature overnight. The next day the reaction was quenched with water and diluted with ethylacetate (3×). The organic layer was separated, washed with brine, dried over sodium sulfate and evaporated in vacuo. The crude oil was purified by silica gel chromatography eluting with 0% EtOAc/100% hexanes to 25% EtOAc/85% hexanes affording (E)-2-bromo-5-fluoro-4-(4-fluorostyryl)pyridine (100 mg, 0.338 mmol, 8.25% yield) as a white solid. 1H-NMR (CDCl3, 400 MHz) δ 8.45 (s, 1H), 8.25 (m, 1H), 7.58-7.57 (m, 2H), 7.36 (d, J=16.0, 1H), 7.15-7.11 (m, 2H), 7.04 (d, J=16.0, 1H), LC/Mass spec. (Analytical HPLC method 2): RT=2.76 min. Mass=295.98 (MH)+.

Workup

  1. customthe flask was purged with oxygen for 3 min
  2. customthe reaction flask was again sealed
  3. custompurged with oxygen for 15 min
  4. stirringThe reaction mixture was then stirred at room temperature overnight
  5. customThe next day the reaction was quenched with water
  6. additiondiluted with ethylacetate (3×)
  7. customThe organic layer was separated
  8. washwashed with brine
  9. dry with materialdried over sodium sulfate
  10. customevaporated in vacuo
  11. customThe crude oil was purified by silica gel chromatography
  12. washeluting with 0% EtOAc/100% hexanes to 25% EtOAc/85% hexanes

Sources & evidence

ORD record
ord-89de008c571843efa5ad0df95f463545
Source dataset
uspto-grants-2014_04
Patent number
US08691821B2

Reaction notes

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