Sodium Carbonate → 2,6-dichloro-4-phenyl-pyridine

HRID 930427Notes

Reaction equation

HRID 930427 reaction equation
Br[C:2]1[CH:7]=[C:6]([Cl:8])[N:5]=[C:4]([Cl:9])[CH:3]=1.[C:10]1(B(O)O)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.O1CCOCC1.C(=O)([O-])[O-].[Na+].[Na+]>O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:8][C:6]1[CH:7]=[C:2]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH:3]=[C:4]([Cl:9])[N:5]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 312751,4-DioxaneHCID 66827Phenylboronic AcidHCID 202807664-Bromo-2,6-dichloropyridine

Product 1

HCID 113220482,6-dichloro-4-phenyl-pyridineYield 26.8%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
80 °C

Procedure

A round-bottomed flask was charged with 4-bromo-2,6-dichloropyridine (Combi-Blocks Inc., 553 mg, 2.437 mmol), phenylboronic acid (446 mg, 3.66 mmol) and trans-dichlorobis(triphenylphosphine)palladium (ii) (27.8 mg, 0.04 mmol). The vial was placed under nitrogen atmosphere using two evacuation/backfill cycles. 1,4-dioxane (12 ml) and sodium carbonate (775 mg, 7.31 mmol) in water (4.1 ml) were added. The reaction mixture was sealed under nitrogen and heated at 80° C. for 1.5 h. The reaction mixture combined with that on pp14 was partitioned between EtOAc and brine. The aqueous layer was back extracted with EtOAc (2×) and the combined EtOAc layers were dried (Na2SO4) and concentrated. The crude material was dissolved in DCM, and purified by chromatography through a Redi-Sep pre-packed silica gel column (40 g), eluting with a gradient of 0% to 20% EtOAc in hexane, to provide 2,6-dichloro-4-phenylpyridine (146 mg, 0.652 mmol, 26.7% yield) as light-yellow oil. MS m/z=224.0 [M]

Workup

  1. customThe reaction mixture was sealed under nitrogen
  2. customwas partitioned between EtOAc and brine
  3. extractionThe aqueous layer was back extracted with EtOAc (2×)
  4. dry with materialthe combined EtOAc layers were dried (Na2SO4)
  5. concentrationconcentrated
  6. dissolutionThe crude material was dissolved in DCM
  7. custompurified by chromatography through a Redi-Sep pre-packed silica gel column (40 g)
  8. washeluting with a gradient of 0% to 20% EtOAc in hexane

Sources & evidence

ORD record
ord-3ba02e77d6e3479c8c183ab018d2d50a
Source dataset
uspto-grants-2016_03
Patent number
US09296734B2

Reaction notes

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