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

HRID 1520634Notes

Reaction equation

HRID 1520634 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]([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: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 178418397HCID 178418397, compoundCatalystHCID 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(0) (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-c201c86c78f2494f9a5108b71a310447
Source dataset
uspto-grants-2015_07
Patent number
US09073855B2

Reaction notes

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