Reaction #65765

Reaction equation

2-amino-3,4-diethoxycarbonyl-6-(4-methoxyethoxymethoxyphenyl)pyridine

sodium nitrite

sodium hydrogencarbonate

→

3,4-Diethoxycarbonyl-6-(4-methoxyethoxymethoxyphenyl)-2-pyridone

Solvents

water

dioxane

hydrochloric acid

dioxane

Conditions

Workup

1. 1
   workup.ADDITIONwas added dropwise under ice-
2. 2
   Temperaturecooling
3. 3
   workup.WAITleft
4. 4
   Otherstanding in a refrigerator overnight
5. 5
   workup.DISTILLATIONwas distilled off
6. 6
   Extractionfollowed by extraction with ethyl acetate
7. 7
   WashThe organic layer was washed with a saturated aqueous solution of sodium chloride
8. 8
   Otherdried
9. 9
   workup.DISTILLATIONThen, the solvent was distilled off
10. 10
    OtherThe residue was purified by silica gel column chromatography (eluent:dichloromethane→ethyl acetate)

Procedure

In 250 ml of 1N hydrochloric acid and 100 ml of dioxane was dissolved 32.2 g of 2-amino-3,4-diethoxycarbonyl-6-(4-methoxyethoxymethoxyphenyl)pyridine, whereto a solution of 6.9 g (1.3 eq.) of sodium nitrite dissolved in 30 ml of water was added dropwise under ice-cooling. The mixture was stirred for 1 hour and left standing in a refrigerator overnight. The mixture was neutralized with sodium hydrogencarbonate, and dioxane was distilled off, followed by extraction with ethyl acetate. The organic layer was washed with a saturated aqueous solution of sodium chloride and dried. Then, the solvent was distilled off. The residue was purified by silica gel column chromatography (eluent:dichloromethane→ethyl acetate).

Source