Hydrochloric Acid → 2-Formyl-3-methyl-1-benzofuran-5-carbonitrile

HRID 2091154Notes

Reaction equation

HRID 2091154 reaction equation
[C:1]([C:3]1[CH:4]=[CH:5][C:6]2[O:10][C:9]([C:11](O)=[O:12])=[C:8]([CH3:14])[C:7]=2[CH:15]=1)#[N:2].C(Cl)(=O)C(Cl)=O.[H-].C(O[Al](OCC(C)C)OCC(C)C)C(C)C.[Li+].Cl>O1CCCC1.CN(C)C=O.[O-2].[O-2].[Mn+4]>[CH:11]([C:9]1[O:10][C:6]2[CH:5]=[CH:4][C:3]([C:1]#[N:2])=[CH:15][C:7]=2[C:8]=1[CH3:14])=[O:12]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 65578Oxalyl chlorideHCID 218445275-Cyano-3-methyl-2-benzofurancarboxylic acidHCID 86662733Lithium tri(isobutoxy)aluminum hydride

Product 1

HCID 824063072-Formyl-3-methyl-1-benzofuran-5-carbonitrileYield 63%

Reagents, catalysts & solvents 3

HCID 6228DimethylformamideCatalystHCID 178418406HCID 178418406, compoundCatalystHCID 8028TetrahydrofuranSolvent4×

Procedure

To 5-cyano-3-methyl-1-benzofuran-2-carboxylic acid (2.58 g) synthesized above in tetrahydrofuran (30 mL) were added oxalyl chloride (1.32 mL) and several drops of N,N-dimethylformamide, and the mixture was stirred at room temperature for 5 hr. The reaction mixture was concentrated under reduced pressure, and the residue was washed with diisopropyl ether to give a pale-brown solid. To a solution (50 mL) of the obtained solid in tetrahydrofuran was added a 1.1M solution (12.0 mL) of lithium tri(isobutoxy)aluminum hydride in tetrahydrofuran at −78° C., and the mixture was stirred at −78° C. for 1.5 hr then at 0° C. for 3 hr. 1N Hydrochloric acid was added to quench the reaction, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over magnesium sulfate, and concentrated under reduced pressure to give a pale-brown solid. To a solution (40 mL) of the obtained solid in tetrahydrofuran was added active manganese dioxide (10.0 g), and the mixture was stirred at 50° C. overnight. Manganese dioxide was filtered off, and the filtrate was concentrated under reduced pressure. The residue was washed with diisopropyl ether to give the title object compound (1.49 g, 63%) as a white solid.

Workup

  1. concentrationThe reaction mixture was concentrated under reduced pressure
  2. washthe residue was washed with diisopropyl ether
  3. customto give a pale-brown solid
  4. stirringthe mixture was stirred at −78° C. for 1.5 hr
  5. waitat 0° C. for 3 hr
  6. customto quench
  7. customthe reaction
  8. extractionthe mixture was extracted with ethyl acetate
  9. washThe extract was washed with saturated brine
  10. dry with materialdried over magnesium sulfate
  11. concentrationconcentrated under reduced pressure
  12. customto give a pale-brown solid
  13. stirringthe mixture was stirred at 50° C. overnight
  14. filtrationManganese dioxide was filtered off
  15. concentrationthe filtrate was concentrated under reduced pressure
  16. washThe residue was washed with diisopropyl ether

Sources & evidence

ORD record
ord-8c27bcbec1a748ac85234a24f4cdbaf1
Source dataset
uspto-grants-2013_05
Patent number
US08436043B2

Reaction notes

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