Sodium Carbonate → 2-(4-Chloro-phenyl)-3-fluoro-pyridine

HRID 1025965Notes

Reaction equation

HRID 1025965 reaction equation
Cl[C:2]1[C:7]([F:8])=[CH:6][CH:5]=[CH:4][N:3]=1.[Cl:9][C:10]1[CH:15]=[CH:14][C:13](B(O)O)=[CH:12][CH:11]=1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.CN(C)C=O.O.C(OCC)(=O)C.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:9][C:10]1[CH:15]=[CH:14][C:13]([C:2]2[C:7]([F:8])=[CH:6][CH:5]=[CH:4][N:3]=2)=[CH:12][CH:11]=1

Participants

8

Reactant 3

HCID 10340Sodium CarbonateHCID 742994-Chlorophenylboronic acidHCID 27827912-Chloro-3-fluoropyridine

Product 1

HCID 666786032-(4-Chloro-phenyl)-3-fluoro-pyridineYield 65.73%

Reagents, catalysts & solvents 4

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 86663138Toluol dimethylformamide waterSolvent

Procedure

A solution of 18.60 g 2-chloro-3-fluoropyridine, 23.25 g 4-chlorophenylboronic acid and 2.30 g 1,1′bis(diphenylphosphino)ferrocenedichloropalladium(II), 22.50 g sodium carbonate in toluol:dimethylformamide:water 190:20:40 and the mixture was stirred at 90° C. over 5 hours. The reaction mixture was diluted with ethyl acetate and water. The phases were separated and the organic phase was washed with brine, dried over magnesium sulfate and evaporated. The residue was purified by chromatography on silica gel with a gradient of heptane to heptane:ethyl acetate 1:1. The product fractions were collected and evaporated. The residue was crystallized in ether to yield 19.30 g (65.73%) of the title compound as off-white solid, MS 208.1 (M+H)+.

Workup

  1. customThe phases were separated
  2. washthe organic phase was washed with brine
  3. dry with materialdried over magnesium sulfate
  4. customevaporated
  5. customThe residue was purified by chromatography on silica gel with a gradient of heptane to heptane:ethyl acetate 1:1
  6. customThe product fractions were collected
  7. customevaporated
  8. customThe residue was crystallized in ether

Sources & evidence

ORD record
ord-71e78ce59dbc4e7b834cef136ca50788
Source dataset
uspto-grants-2014_05
Patent number
US08729105B2

Reaction notes

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