Ammonia → 5-Formyl-6-methoxy-3-pyridinecarbonitrile

HRID 1837714Notes

Reaction equation

HRID 1837714 reaction equation
CO[CH:3]([O:13]C)[C:4]1[C:5]([O:11][CH3:12])=[N:6][CH:7]=[C:8](Br)[CH:9]=1.[C-:15]#[N:16].[Na+].N.Cl.C(=O)([O-])[O-].[Na+].[Na+]>C(#N)CC.CC(C)=O.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>[C:15]([C:8]1[CH:9]=[C:4]([CH:3]=[O:13])[C:5]([O:11][CH3:12])=[N:6][CH:7]=1)#[N:16]

Participants

9

Reactant 5

HCID 222AmmoniaHCID 313Hydrochloric AcidHCID 8929Sodium CyanideHCID 10340Sodium CarbonateHCID 22678608HCID 22678608, compound

Product 1

HCID 226786735-Formyl-6-methoxy-3-pyridinecarbonitrileYield 68.1%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 180AcetoneSolventHCID 7854PropionitrileSolvent

Conditions

Temperature
100 °C

Procedure

2.00 g of 5-bromo-2-methoxy-3-pyridinecarboxaldehyde dimethyl acetal was dissolved in 25 ml of propionitrile. To the mixture were added 449 mg of sodium cyanide, 152 mg of cuprous iodide and 462 mg of tetrakis(triphenylphosphine)palladium, followed by stirring at 100° C. for 45 minutes in nitrogen atmosphere. A diluted ammonia was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and brine, and then dried over anhydrous magnesium sulfate. The solvent was evaporated, to give an oil. The oil was dissolved in 16 ml of acetone, 4 ml of 5N-hydrochloric acid was added thereto, and the mixture was left for 30 minutes at room temperature. An aqueous sodium carbonate aqueous solution was added to the reaction solution, and the mixture was extracted with ethyl acetate. The organic layer was washed with water and brine, and then dried over anhydrous magnesium sulfate. The solvent was evaporated, and the crude product was purified by silica gel column chromatography (toluene:ethyl acetate=1:1), to give 843 mg of the title compound as white crystals.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with water and brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customThe solvent was evaporated
  5. customto give an oil
  6. waitthe mixture was left for 30 minutes at room temperature
  7. extractionthe mixture was extracted with ethyl acetate
  8. washThe organic layer was washed with water and brine
  9. dry with materialdried over anhydrous magnesium sulfate
  10. customThe solvent was evaporated
  11. customthe crude product was purified by silica gel column chromatography (toluene:ethyl acetate=1:1)

Sources & evidence

ORD record
ord-8971683554db45fd958b06e1be245f9c
Source dataset
uspto-grants-2004_08
Patent number
US06784192B2

Reaction notes

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