Reacción #50147

Ecuación de reacción

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

Rendimiento 67.5%

Disolventes

dichloromethane

Condiciones de reacción

Tratamiento posterior

1. 1
   LavadoThe reaction mixture is washed with water
2. 2
   Secadodried over sodium sulfate
3. 3
   Otroevaporated
4. 4
   workup.DISSOLUTIONThe residue is dissolved in ethanol (30 ml)
5. 5
   workup.ADDITIONfumaric acid (2.00 g) is added
6. 6
   Temperaturathe solution is refluxed for three hours
7. 7
   OtroThe solvent is evaporated
8. 8
   workup.ADDITIONthe residue is treated with a saturated sodium hydrogen carbonate solution
9. 9
   Extracciónextracted with chloroform
10. 10
    OtroThe organic layer is dried
11. 11
    Otroevaporated
12. 12
    OtroPurification by silica gel column chromatography (solvent; chloroform/methanol)

Procedimiento

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.

Fuente