Sodium Carbonate → 4-(4-Chlorophenyl)-2-fluoro-5-methylpyridine

HRID 629620

Reaction equation

HRID 629620 reaction equation
[F:1][C:2]1[CH:7]=[C:6](I)[C:5]([CH3:9])=[CH:4][N:3]=1.[Cl:10][C:11]1[CH:16]=[CH:15][C:14](B(O)O)=[CH:13][CH:12]=1.C(=O)([O-])[O-].[Na+].[Na+]>C(O)C.O.C1(C)C=CC=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Pd]>[Cl:10][C:11]1[CH:16]=[CH:15][C:14]([C:6]2[C:5]([CH3:9])=[CH:4][N:3]=[C:2]([F:1])[CH:7]=2)=[CH:13][CH:12]=1

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 742994-Chlorophenylboronic acidHCID 100600522-Fluoro-4-iodo-5-methylpyridine

Product 1

HCID 672259184-(4-Chlorophenyl)-2-fluoro-5-methylpyridine

Reagents, catalysts & solvents 4

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolvent

Procedure

A mixture of 2-fluoro-4-iodo-5-methylpyridine (1.9 g), 4-chlorophenylboronic acid (1.504 g), tetrakis(triphenylphosphine)palladium(O) (0.463 g), and sodium carbonate (2.55 g) in ethanol (20 mL), water (10 mL) and toluene (10 mL) was heated under reflux for 6 hours. The reaction mixture was partitioned between ethyl acetate and water. The organic layer was separated, and the aqueous layers were extracted with additional ethyl acetate three times. The combined organic layers were washed with brine, dried over MgSO4, filtered, and concentrated. The residue was purified with flash column chromatography on silica gel using 5% ethyl acetate in hexanes to give the title compound.

Workup

  1. temperaturewas heated
  2. temperatureunder reflux for 6 hours
  3. customThe reaction mixture was partitioned between ethyl acetate and water
  4. customThe organic layer was separated
  5. extractionthe aqueous layers were extracted with additional ethyl acetate three times
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe residue was purified with flash column chromatography on silica gel using 5% ethyl acetate in hexanes

Sources & evidence

ORD record
ord-ff18ae5ba90d4ef6987b1811c16a1437
Source dataset
uspto-grants-2016_04
Patent number
US09315488B2

Linked notes

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