Ethyl 6-methylnicotinate → 6-Methyl-α-[4-(methylthio)phenyl]-β-oxo-3-pyridinepropanenitrile

HRID 413470

Reaction equation

HRID 413470 reaction equation
[CH3:1][C:2]1[CH:12]=[CH:11][C:5]([C:6]([O:8]CC)=O)=[CH:4][N:3]=1.C[O-].[Na+].[CH3:16][S:17][C:18]1[CH:23]=[CH:22][C:21]([CH2:24][C:25]#[N:26])=[CH:20][CH:19]=1>C1(C)C=CC=CC=1>[CH3:16][S:17][C:18]1[CH:23]=[CH:22][C:21]([CH:24]([C:25]#[N:26])[C:6]([C:5]2[CH:4]=[N:3][C:2]([CH3:1])=[CH:12][CH:11]=2)=[O:8])=[CH:20][CH:19]=1

Participants

5

Reactant 3

HCID 281994Ethyl 6-methylnicotinateHCID 27600872-(4-(Methylthio)phenyl)acetonitrileHCID 10942334Sodium Methoxide

Product 1

HCID 113005426-Methyl-α-[4-(methylthio)phenyl]-β-oxo-3-pyridinepropanenitrile

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

Under an atmosphere of nitrogen, a mixture of 38.5 g (250 mmol) of ethyl 6-methylnicotinate, 29.9 g (500 mmol) of sodium methoxide (90.5%) and 300 ml of toluene was added, at 85-90° C. and over the course of 30 min, to a solution of 47.3 g (250 mmol) of 4-(methylthio)phenylacetonitrile in 75 ml of toluene. This mixture was stirred under reflux for 14 h, then distilled until the overhead temperature exceeded 110° C. and kept at reflux for another 6 h. The reaction mixture was poured into 500 g of ice water, the organic phase was decanted off and the aqueous phase was extracted with 3×100 ml of toluene. The aqueous phase was acidified to pH 6.0 using conc. HCl. The resulting yellow-beige suspension was filtered and the residue was washed with water and dried. This gave 53.9 g (76%) of the title product in the form of a yellow solid.

Workup

  1. temperatureunder reflux for 14 h
  2. distillationdistilled until the overhead temperature
  3. customexceeded 110° C.
  4. temperatureat reflux for another 6 h
  5. additionThe reaction mixture was poured into 500 g of ice water
  6. customthe organic phase was decanted off
  7. extractionthe aqueous phase was extracted with 3×100 ml of toluene
  8. filtrationThe resulting yellow-beige suspension was filtered
  9. washthe residue was washed with water
  10. customdried

Sources & evidence

ORD record
ord-d2fbf46e21984939a9c3ace70bf669b7
Source dataset
uspto-grants-2003_05
Patent number
US06566527B1

Linked notes

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