Ethyl cyanoacetate → HCID 14796138, compound

HRID 2074036Notes

Reaction equation

HRID 2074036 reaction equation
[H-].[Na+].[C:3]([CH2:5][C:6]([O:8][CH2:9][CH3:10])=[O:7])#[N:4].[H][H].CS(O[CH2:18][CH2:19][CH2:20][CH2:21][C:22]1[CH:23]=[C:24]([C:27]([O:29][CH3:30])=[O:28])[S:25][CH:26]=1)(=O)=O>O1CCCC1>[C:3]([CH:5]([C:6]([O:8][CH2:9][CH3:10])=[O:7])[CH2:18][CH2:19][CH2:20][CH2:21][C:22]1[CH:23]=[C:24]([C:27]([O:29][CH3:30])=[O:28])[S:25][CH:26]=1)#[N:4]

Participants

6

Reactant 4

HCID 7764Ethyl cyanoacetateHCID 24758Sodium hydrideHCID 14796136HCID 14796136, compoundHCID 178418361HCID 178418361, compound

Product 1

HCID 14796138HCID 14796138, compoundYield 47.7%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A 250 Ml three-neck round bottom flask, equipped with a magnetic stirrer, reflux condenser, addition funnel, and gas inlet, was charged with 0.59 g (1.1 eq) of 60% sodium hydride and flame dried under a nitrogen atmosphere. After cooling to room temperature, mineral oil was removed by washing twice with anhydrous tetrahydrofuran and 100 mL of anhydrous tetrahydrofuran were then added. This mixture was brought to 0° C. on an ice bath and an anhydrous tetrahydrofuran solution of 1.52 g (1.0 eq) of ethyl cyanoacetate was added dropwise under a nitrogen atmosphere with moderation of evolution of hydrogen gas. The mixture was stirred vigorously while warming to room temperature until gas evolution was no longer observed. To this mixture, an anhydrous tetrahydrofuran solution of 3.92 g (1.0 eq) of methyl 4-(4-methylsulfonyloxybutyl)thien-2-ylcarboxylate was added dropwise. The resulting mixture was refluxed with stirring under a nitrogen atmosphere for 24 hours. After cooling to room temperature, solvent was removed under reduced pressure and diethyl ether was added to the residue. The organic extract was washed with water, brine, dried (magnesium sulfate), filtered and concentrated under reduced pressure. The residue was purified by flash chromatography eluting with 1:1 ethyl acetate:hexanes. Fractions homogeneous by thin layer chromatography for the major component were combined and concentrated under reduced pressure to give 1.98 g (47.7%) of pure methyl 4-(5-cyano-5-carbethoxypentyl)thien-2-carboxylate as a clear oil; IR (KBr, cm-1): 1746, 1711, 1444, 1260, 1225, 1220, 1207; UV (Ethanol): μmax =280 nm (epsilon=5940), 248 nm (epsilon=9290); 1H NMR (CDCl3, 300 MHz) delta 7.60 (s, 1H), 7.15 (s, 1H), 4.23, (q, J=7.2 Hz, 2H), 3.85 (s, 3H), 3.47 (t, J=6.9 Hz, 1H), 2.62 (t, J=7.5 Hz, 2H), 1.95 (q, J=7.3 Hz, 2H), 1.62-1.69 (m, 2H), 1.48-1.47 (m, 2H), 1.27-1.33 (m, 3H); MASS: M+ =309 (FD).

Workup

  1. customA 250 Ml three-neck round bottom flask, equipped with a magnetic stirrer
  2. temperaturereflux
  3. additioncondenser, addition funnel, and gas inlet
  4. temperatureflame
  5. customdried under a nitrogen atmosphere
  6. custommineral oil was removed
  7. washby washing twice with anhydrous tetrahydrofuran and 100 mL of anhydrous tetrahydrofuran
  8. additionwere then added
  9. customThis mixture was brought to 0° C. on an ice bath
  10. temperaturewhile warming to room temperature until gas evolution
  11. temperatureThe resulting mixture was refluxed
  12. stirringwith stirring under a nitrogen atmosphere for 24 hours
  13. temperatureAfter cooling to room temperature
  14. customsolvent was removed under reduced pressure and diethyl ether
  15. additionwas added to the residue
  16. extractionThe organic extract
  17. washwas washed with water, brine
  18. dry with materialdried (magnesium sulfate)
  19. filtrationfiltered
  20. concentrationconcentrated under reduced pressure
  21. customThe residue was purified by flash chromatography
  22. washeluting with 1:1 ethyl acetate
  23. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-32684de76803415596a32070f9b528a1
Source dataset
uspto-grants-1990_04
Patent number
US04920125

Reaction notes

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