Potassium Carbonate → 5-Chloro-3-(4-chlorophenyl)-2-fluoropyridine

HRID 1958143Notes

Reaction equation

HRID 1958143 reaction equation
Br[C:2]1[C:3]([F:9])=[N:4][CH:5]=[C:6]([Cl:8])[CH:7]=1.[Cl:10][C:11]1[CH:16]=[CH:15][C:14](B(O)O)=[CH:13][CH:12]=1.C(=O)([O-])[O-].[K+].[K+]>O.C1COCC1.C(OCC)(=O)C>[Cl:8][C:6]1[CH:7]=[C:2]([C:14]2[CH:15]=[CH:16][C:11]([Cl:10])=[CH:12][CH:13]=2)[C:3]([F:9])=[N:4][CH:5]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 742994-Chlorophenylboronic acidHCID 404270103-Bromo-5-chloro-2-fluoropyridine

Product 1

HCID 666785965-Chloro-3-(4-chlorophenyl)-2-fluoropyridineYield 95.7%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 3-bromo-5-chloro-2-fluoro-pyridine, (CAN 884494-87-5; 2.0 g, 9.50 mmol), 4-chlorophenylboronic acid (CAN 1679-18-1; 1.5 g, 9.50 mmol); tetrakis(triphenylphoshine)-palladium (0.55 g, 0.48 mmol) and potassium carbonate (2.6 g, 19 mmol) in water (50 mL) and THF (50 mL) was heated at reflux temperature for 18 h. The reaction mixture was cooled, diluted with ethyl acetate, phases were separated and the water phase was extracted with ethyl acetate. The organic phases were pooled, dried with MgSO4 and the solvent was removed in vacuo. The residue was purified by column chromatography (on silica gel with a gradient of heptane to heptane:ethyl acetate=9:1 to yield the title product (2.2 g, 95%) as white solid; MS (ESI): 241.0 (M)+.

Workup

  1. temperatureat reflux temperature for 18 h
  2. temperatureThe reaction mixture was cooled
  3. customwere separated
  4. extractionthe water phase was extracted with ethyl acetate
  5. dry with materialdried with MgSO4
  6. customthe solvent was removed in vacuo
  7. customThe residue was purified by column chromatography (on silica gel with a gradient of heptane to heptane

Sources & evidence

ORD record
ord-8ca50a4a9a884077924a13b824a73225
Source dataset
uspto-grants-2013_04
Patent number
US08410107B2

Reaction notes

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