p-Toluenesulfonic acid → 5-NITRO-2-PYRIDINEACETONITRILE

HRID 1518195Notes

Reaction equation

HRID 1518195 reaction equation
[N+:1]([C:4]1[CH:5]=[CH:6][C:7](Cl)=[N:8][CH:9]=1)([O-:3])=[O:2].C([O-])([O-])=O.[K+].[K+].C(OC(=O)[CH2:23][C:24]#[N:25])(C)(C)C.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1COCC1>[N+:1]([C:4]1[CH:5]=[CH:6][C:7]([CH2:23][C:24]#[N:25])=[N:8][CH:9]=1)([O-:3])=[O:2]

Participants

6

Reactant 4

HCID 6101p-Toluenesulfonic acidHCID 11430Potassium CarbonateHCID 70693tert-Butyl cyanoacetateHCID 783082-Chloro-5-nitropyridine

Product 1

HCID 120149655-NITRO-2-PYRIDINEACETONITRILEYield 66%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 5-nitro-2-chloropyridine (18 g, 113.5 mmol) in THF (100 ml) at room temperature K2CO3 (39.2 g, 283.8 mmol), cyanoacetic acid tert-butyl ester (24 g, 170.30 mmol) and 4 Å molecular sieves were added. The mixture was heated to reflux and stirred for 20 h. After concentrating the mixture under reduced pressure the residue was partitioned between ethyl acetate and saturated aqueous NaHCO3. The organic layer was washed with brine, dried over MgSO4, filtered and the solvent evaporated under reduced pressure. The obtained oil was dissolved in toluene (300 ml), toluene-4-sulfonic acid (2 g, 11.6 mmol) was added, and the mixture was heated to reflux for 2 h. The mixture then was stirred at room temperature for 16 h. After which the mixture was concentrated under reduced pressure. The residue was partitioned between ethyl acetate and water. The aqueous layer was extracted with ethyl acetate and the combined organic layers were washed with brine, dried over MgSO4, filtered, and the solvent evaporated under reduced pressure. Column chromatography (cyclohexane/dichloromethane, 4/1) gave the product as a colorless oil (10.3 g, 66%).

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux
  3. concentrationAfter concentrating the mixture under reduced pressure the residue
  4. customwas partitioned between ethyl acetate and saturated aqueous NaHCO3
  5. washThe organic layer was washed with brine
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. customthe solvent evaporated under reduced pressure
  9. dissolutionThe obtained oil was dissolved in toluene (300 ml)
  10. temperaturethe mixture was heated
  11. temperatureto reflux for 2 h
  12. stirringThe mixture then was stirred at room temperature for 16 h
  13. concentrationAfter which the mixture was concentrated under reduced pressure
  14. customThe residue was partitioned between ethyl acetate and water
  15. extractionThe aqueous layer was extracted with ethyl acetate
  16. washthe combined organic layers were washed with brine
  17. dry with materialdried over MgSO4
  18. filtrationfiltered
  19. customthe solvent evaporated under reduced pressure

Sources & evidence

ORD record
ord-8621e2c879134a79a4deb37d7dcd335f
Source dataset
uspto-grants-2012_07
Patent number
US08232426B2

Reaction notes

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