Réaction #50147

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-(3-dimethylaminopropyl)-3-ethylcarbodiimide 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
   workup.DISSOLUTIONThe residue is dissolved in ethanol (30 ml)
5. 5
   workup.ADDITIONfumaric acid (2.00 g) is added
6. 6
   Températurethe solution is refluxed for three hours
7. 7
   AutreThe solvent is evaporated
8. 8
   workup.ADDITIONthe residue is treated with a saturated sodium hydrogen carbonate solution
9. 9
   Extractionextracted with chloroform
10. 10
    AutreThe organic layer is dried
11. 11
    Autreevaporated
12. 12
    AutrePurification by silica gel column chromatography (solvent; chloroform/methanol)

Mode opératoire

A solution of 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-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.80 g), triethylamine (1.40 g) in dichloromethane (20 ml) is stirred overnight at room temperature. The reaction mixture is washed with water and dried over sodium sulfate, and then evaporated. The residue is dissolved in ethanol (30 ml), fumaric acid (2.00 g) is added, and the solution is refluxed for three hours. The solvent is evaporated and the residue is treated with a saturated sodium hydrogen carbonate solution and then extracted with chloroform. The organic layer is dried and evaporated. Purification by silica gel column chromatography (solvent; chloroform/methanol) gives 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 a foam.

Source