Diethyl Succinate → 3-(Ethoxycarbonyl)-4-(5-methyl-3-thienyl)but-3-enoic Acid

HRID 1177302Notes

Reaction equation

HRID 1177302 reaction equation
CC[O-].[Na+].[CH3:5][C:6]1[S:10][CH:9]=[C:8]([CH:11]=O)[CH:7]=1.[C:13]([O:22]CC)(=[O:21])[CH2:14][CH2:15][C:16]([O:18][CH2:19][CH3:20])=[O:17]>C(O)C>[CH2:19]([O:18][C:16]([C:15](=[CH:11][C:8]1[CH:7]=[C:6]([CH3:5])[S:10][CH:9]=1)[CH2:14][C:13]([OH:22])=[O:21])=[O:17])[CH3:20]

Participants

5

Reactant 3

HCID 31249Diethyl SuccinateHCID 2723922Sodium ethoxideHCID 65020115-Methylthiophene-3-carbaldehyde

Product 1

HCID 667555563-(Ethoxycarbonyl)-4-(5-methyl-3-thienyl)but-3-enoic AcidYield 60%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

Sodium ethylate (17 g, 0.24 mol) was added under vigorous stirring to a solution of 5-methylthiophene-3-carbaldehyde (26 g 90% purity, 0.20 mol) and diethyl succinate (54 g, 0.31 mol) in ethanol (400 mL). The reaction mixture was refluxed for 3 h and evaporated in vacuum (˜20 mmHg) at 50° C. until the solvent distillation ceased. The obtained residue was diluted with 300 mL of 10% HCl and 500 mL of ethyl acetate. The mixture was shaken. The organic layer was separated, diluted with 700 mL of a saturated aqueous solution of NaHCO3, and shaken. The aqueous layer was separated, neutralized by 10% HCl to pH 2, and subjected to extraction by 1 L of ethyl acetate. The organic layer was evaporated in vacuum (˜20 mmHg) at 60° C. The residue was chromatographed on a layer of silica gel (200×150 mm) with hexane/ethyl acetate mixture (1:1). Fractions with the target product were collected and evaporated in vacuum to give the desired product 30 g (0.12 mol, 57%) as an oil.

Workup

  1. temperatureThe reaction mixture was refluxed for 3 h
  2. customevaporated in vacuum (˜20 mmHg) at 50° C. until the solvent distillation
  3. additionThe obtained residue was diluted with 300 mL of 10% HCl and 500 mL of ethyl acetate
  4. customThe organic layer was separated
  5. additiondiluted with 700 mL of a saturated aqueous solution of NaHCO3
  6. stirringshaken
  7. customThe aqueous layer was separated
  8. extractionsubjected to extraction by 1 L of ethyl acetate
  9. customThe organic layer was evaporated in vacuum (˜20 mmHg) at 60° C
  10. customThe residue was chromatographed on a layer of silica gel (200×150 mm) with hexane/ethyl acetate mixture (1:1)
  11. customFractions with the target product were collected
  12. customevaporated in vacuum

Sources & evidence

ORD record
ord-db1fe1f1681b47a29491a7c5483ef8a7
Source dataset
uspto-grants-2010_11
Patent number
US07842713B2

Reaction notes

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