1,2-Dimethoxyethane → 4-chloro-2-phenylpyridine

HRID 1897980Notes

Reaction equation

HRID 1897980 reaction equation
Cl[C:2]1[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][N:3]=1.[C:9]1(B(O)O)[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.C(=O)([O-])[O-].[K+].[K+].C(COC)OC>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.O>[C:9]1([C:2]2[CH:7]=[C:6]([Cl:8])[CH:5]=[CH:4][N:3]=2)[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 11430Potassium CarbonateHCID 335152,4-DichloropyridineHCID 66827Phenylboronic Acid

Product 1

HCID 27628464-chloro-2-phenylpyridineYield 62.4%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Procedure

2,4-dichloropyridine (10 g, 67.57 mmol), phenylboronic acid (9.0 g, 74.32 mmol), and potassium carbonate (28 g, 202.70 mmol), 300 mL dimethoxyethane and 30 mL of water was placed in a 1 L round-bottom flask. Nitrogen was bubbled directly into the mixture for 30 min. Tetrakis(triphenylphosphine)palladium(0) (780 mg, 0.675 mmol) was added and nitrogen was bubbled into the reaction mixture for a another 15 min. The reaction mixture was then heated to reflux under nitrogen for 16 h. The reaction was then allowed to cool to room temperature and diluted with ethyl acetate and water. The organic and aqueous layers were separated and the aqueous layer was extracted with ethyl acetate. The organic layers were combined and washed with a saturated brine solution. The organic layer was then dried over magnesium sulfate, filtered, and the solvent was removed under vacuum to give an off-white solid as crude. The crude was purified by column chromatography using silica gel as the stationary phase and 2% ethyl acetate in hexanes as the mobile phase. 8.0 g of desired product was obtained after purification (54% yield). 11.5 g of desired product was obtained after purification (89.77% yield).

Workup

  1. customNitrogen was bubbled directly into the mixture for 30 min
  2. customnitrogen was bubbled into the reaction mixture for a another 15 min
  3. temperatureThe reaction mixture was then heated
  4. temperatureto reflux under nitrogen for 16 h
  5. additiondiluted with ethyl acetate and water
  6. customThe organic and aqueous layers were separated
  7. extractionthe aqueous layer was extracted with ethyl acetate
  8. washwashed with a saturated brine solution
  9. dry with materialThe organic layer was then dried over magnesium sulfate
  10. filtrationfiltered
  11. customthe solvent was removed under vacuum
  12. customto give an off-white solid as crude
  13. customThe crude was purified by column chromatography

Sources & evidence

ORD record
ord-fa6968b2c1954ac1987dfdbf8b4a687c
Source dataset
uspto-grants-2013_08
Patent number
US08519384B2

Reaction notes

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