Reaction #452138

Reaction equation

Ethyl 4,4-diethoxy-2-(3-nitrophenylmethylene)-3-oxobutanoate

ethyl 3-amino-4-fluoro-2-butenoate

→

title compound

Yield 18.3%

Diethyl 2-(fluoromethyl)-6-formyl-1,4-dihydro-4-(3-nitrophenyl)-3,5-pyridinedicarboxylate

Yield 18.3%

Solvents

ethyl acetate

Conditions

Workup

1. 1
   Washwashed with water and saturated brine
2. 2
   Dryingdried (MgSO4)
3. 3
   Otherthe solvent was removed in vacuo
4. 4
   workup.DISSOLUTIONThe residue was dissolved in tetrahydrofuran (195 ml)
5. 5
   workup.ADDITION50% aqueous hydrochloric acid (292 ml) was added slowly
6. 6
   ExtractionAfter 30 minutes the reaction mixture was extracted with ethyl acetate
7. 7
   Extractionthe organic extract
8. 8
   Washwashed with saturated aqueous sodium bicarbonate, water
9. 9
   Dryingdried (MgSO4)
10. 10
    Otherthe solvent was removed in vacuo
11. 11
    OtherThe residue was chromatographed on silica eluting with ethyl acetate/petroleum ether (60°-80°) mixtures
12. 12
    OtherCrystallisation from 2-propanol

Procedure

Ethyl 4,4-diethoxy-2-(3-nitrophenylmethylene)-3-oxobutanoate (21.75 g, 62 mmoles) and ethyl 3-amino-4-fluoro-2-butenoate (9.17 g, 68 mmoles) were heated at 125° for 1.5 hours. The reaction mixture was dissolved in ethyl acetate (150 ml), washed with water and saturated brine, dried (MgSO4) and the solvent was removed in vacuo. The residue was dissolved in tetrahydrofuran (195 ml) and 50% aqueous hydrochloric acid (292 ml) was added slowly. After 30 minutes the reaction mixture was extracted with ethyl acetate and the organic extract washed with saturated aqueous sodium bicarbonate, water, dried (MgSO4) and the solvent was removed in vacuo. The residue was chromatographed on silica eluting with ethyl acetate/petroleum ether (60°-80°) mixtures. Crystallisation from 2-propanol gave the title compound (4.6 g), mp 88°-90°.

Source