Ethyl Acetate → 3-Methyl-4-pyridinecarboxaldehyde

HRID 1005376Notes

Reaction equation

HRID 1005376 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].C(OCC)(=O)C.[CH3:13][C:14]1[CH:29]=[N:28][CH:27]=[CH:26][C:15]=1[C:16](N(C)C1C=CC=CC=1)=[O:17].C(C(C(C([O-])=O)O)O)([O-])=O.[K+].[K+]>O1CCCC1.CO>[CH3:13][C:14]1[CH:29]=[N:28][CH:27]=[CH:26][C:15]=1[CH:16]=[O:17]

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 6100505Dipotassium 2,3-dihydroxybutanedioateHCID 13115137N,3-Dimethyl-N-phenylpyridine-4-carboxamideHCID 21226445Aluminium lithium hydride

Product 1

HCID 15018803-Methyl-4-pyridinecarboxaldehydeYield 70%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 8028TetrahydrofuranSolvent2×

Procedure

1M Lithium aluminium hydride in tetrahydrofuran (6.96 ml, 6.96 mmol) in anhydrous tetrahydrofaran (15 ml) under a nitrogen atmosphere, was cooled to -10° C. and treated with ethyl acetate (0.61 g, 6.96 mmol) dropwise. After 10 minutes this solution was treated with dropwise addition of 3,N-dimethyl-N-phenyl-isonicotinamide (1.50 g, 6.63 mmol, J. Chem. Res., Synop. 1986, 20-21) in tetrahydrofuran (15 ml). After 2 hours at -10° C. the mixture was allowed to warm to room temperature. Methanol (10 ml) was added, followed by a saturated solution of potassium tartrate. The organic layer was separated and the aqueous layer was exhaustively extracted with dichloromethane. The combined organics were washed with water (2×10 ml), dried (sodium sulphate) then evaporated. The residue was purified by chromatography on silica using dichloromethane/methanol (40:1) to afford the aldehyde (560 mg, 70%) as a gum. MS, ES+, m/z=122 for (M+H)+, δH (360 MHz, DMSO-d6) 2.59 (3H, s), 7.68 (1H, d, J=5 Hz), 8.66 (1H, s), 8.70 (1H, d, J=5 Hz), 10-30 (1H, s).

Workup

  1. customThe organic layer was separated
  2. extractionthe aqueous layer was exhaustively extracted with dichloromethane
  3. washThe combined organics were washed with water (2×10 ml)
  4. dry with materialdried (sodium sulphate)
  5. customthen evaporated
  6. customThe residue was purified by chromatography on silica

Sources & evidence

ORD record
ord-e12154c11fa44c4ba9738b3698f0b867
Source dataset
uspto-grants-2000_04
Patent number
US06054469

Reaction notes

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