Réaction #413644

Équation de réaction

Ethyl 2-ethyl-3-{2'-(1-trityl-1H-tetrazol-5-yl)biphenyl-4-yl}methyl-4,5,6,7-tetrahydroimidazo[4,5-c]-pyridine-4-carboxylate

monoethyl malonate

1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride

triethylamine

→

ethyl 2-ethyl-3-{2'-(1H-tetrazol-5-yl)biphenyl-4-yl}methyl-5-ethoxycarbonylacetyl-4,5,6,7-tetrahydroimidazo[4,5-c]pyridine-4-carboxylate

Rendement 67.5%

Solvants

dichloromethane

Conditions de réaction

Traitement

1. 1
   LavageThe reaction mixture is washed with water
2. 2
   Séchagedried over sodium sulfate
3. 3
   Autreevaporated
4. 4
   Autreto remove the solvent
5. 5
   workup.DISSOLUTIONThe residue is dissolved in ethanol (30 ml)
6. 6
   workup.ADDITIONis added fumaric acid (2.00 g)
7. 7
   TempératureThe mixture is refluxed for three hours
8. 8
   Autreevaporated
9. 9
   Autreto remove the solvent
10. 10
    workup.ADDITIONThe resulting residue is treated with a saturated sodium hydrogen carbonate solution
11. 11
    Extractionextracted with chloroform
12. 12
    AutreThe organic layer is dried
13. 13
    Autreevaporated
14. 14
    Autreto remove the solvent
15. 15
    AutreThe resulting residue is purified by silica gel column chromatography (solvent; chloroform/methanol)

Mode opératoire

Ethyl 2-ethyl-3-{2'-(1-trityl-1H-tetrazol-5-yl)biphenyl-4-yl}methyl-4,5,6,7-tetrahydroimidazo[4,5-c]-pyridine-4-carboxylate (1.94 g), monoethyl malonate (0.74 g), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (0.80 g), and triethylamine (1.40 g) are dissolved in dichloromethane (20 ml). The mixture is stirred overnight at room temperature. The reaction mixture is washed with water, dried over sodium sulfate, and then evaporated to remove the solvent. The residue is dissolved in ethanol (30 ml) and thereto is added fumaric acid (2.00 g). The mixture is refluxed for three hours and evaporated to remove the solvent. The resulting residue is treated with a saturated sodium hydrogen carbonate solution and extracted with chloroform. The organic layer is dried and evaporated to remove the solvent. The resulting residue is purified by silica gel column chromatography (solvent; chloroform/methanol) to give ethyl 2-ethyl-3-{2'-(1H-tetrazol-5-yl)biphenyl-4-yl}methyl-5-ethoxycarbonylacetyl-4,5,6,7-tetrahydroimidazo[4,5-c]pyridine-4-carboxylate (1.07 g) as foam.

Source