Sodium Carbonate → 2-Chloro-4-(4-fluoro-2-methoxyphenyl)pyridine

HRID 2176870Notes

Reaction equation

HRID 2176870 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5](B(O)O)=[C:4]([O:11][CH3:12])[CH:3]=1.C(=O)([O-])[O-].[Na+].[Na+].Br[C:20]1[CH:25]=[CH:24][N:23]=[C:22]([Cl:26])[CH:21]=1>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:26][C:22]1[CH:21]=[C:20]([C:5]2[CH:6]=[CH:7][C:2]([F:1])=[CH:3][C:4]=2[O:11][CH3:12])[CH:25]=[CH:24][N:23]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 2782672(4-Fluoro-2-methoxyphenyl)boronic acidHCID 38477704-Bromo-2-chloropyridine

Product 1

HCID 584326092-Chloro-4-(4-fluoro-2-methoxyphenyl)pyridineYield 73.4%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

To a solution of 4-fluoro-2-methoxyphenylboronic acid (440 mg, 2.58 mmol) in 8 ml of 1,4-dioxane was added 2.5 ml of saturated aqueous sodium carbonate solution. Argon gas was purged for 30 min at room temperature. 4-Bromo-2-chloropyridine (500 mg, 2.58 mmol) and tetrakis(triphenylphosphine)palladium (0) (150 mg, 0.129 mmol) were added to reaction mixture simultaneously and argon gas was bubbled for another 40 min. The reaction mixture was heated to reflux for 16 h, TLC confirms completion of reaction and the mixture was concentrated under reduced pressure. The residue was partitioned between DCM and water. The organic layer was separated, washed with brine, water, dried (Na2SO4) and concentrated. The obtained crude residue was purified through silica gel column chromatography eluting with 15% ethyl acetate in DCM to provide 2-chloro-4-(4-fluoro-2-methoxyphenyl)pyridine (450 mg, 73.3%).

Workup

  1. customArgon gas was purged for 30 min at room temperature
  2. customargon gas was bubbled for another 40 min
  3. temperatureThe reaction mixture was heated
  4. temperatureto reflux for 16 h
  5. customcompletion of reaction
  6. concentrationthe mixture was concentrated under reduced pressure
  7. customThe residue was partitioned between DCM and water
  8. customThe organic layer was separated
  9. washwashed with brine, water
  10. dry with materialdried (Na2SO4)
  11. concentrationconcentrated
  12. customThe obtained crude residue
  13. customwas purified through silica gel column chromatography
  14. washeluting with 15% ethyl acetate in DCM

Sources & evidence

ORD record
ord-7b09360214584f919d1370fc7ae78969
Source dataset
uspto-grants-2015_06
Patent number
US09067888B2

Reaction notes

Loading…