Реакция #633942

Уравнение реакции

sodium bicarbonate

Methyl dichlorophosphate

(E)-3-[6-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl]acrylamide

1,8-diazabicyclo[5,4,0]-7-undecene

→

title compound

Выход 85.8%

(E)-3-[6-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl]acrylonitrile

Выход 85.8%

Растворители

Water

methylene chloride

Условия реакции

Обработка

1. 1
   Температураcooling over 20 minutes
2. 2
   workup.STIRRINGthe reaction solution was stirred at room temperature for 10 minutes
3. 3
   ФильтрацияThen, the reaction solution was filtered
4. 4
   Другоеthe organic layer in the filtrate was separated
5. 5
   СушкаThe combined organic layers were dried over anhydrous magnesium sulfate
6. 6
   Другоеpurified by short silica gel column chromatography (carrier: Chromatorex NH; elution solvent: methylene chloride)
7. 7
   КонцентрированиеThe eluted fraction was concentrated
8. 8
   ДругоеThe resulting residue was triturated with ethyl acetate and tert-butyl methyl ether
9. 9
   Другоеdried under reduced pressure overnight

Методика

Methyl dichlorophosphate (33 ml) was added dropwise to a suspension of (E)-3-[6-methoxy-5-(4-methyl-1H-imidazol-1-yl)pyridin-2-yl]acrylamide (42.96 g) and 1,8-diazabicyclo[5,4,0]-7-undecene (112 ml) in methylene chloride (400 ml) under ice-cooling over 20 minutes. The reaction solution was stirred at the same temperature for 10 minutes and at room temperature for further 35 minutes. Then, a saturated sodium bicarbonate solution (200 ml) was added to the reaction solution, and the reaction solution was stirred at room temperature for 10 minutes. Water was added to the reaction solution. Then, the reaction solution was filtered and the organic layer in the filtrate was separated. The aqueous layer was reextracted with methylene chloride (twice). The combined organic layers were dried over anhydrous magnesium sulfate and purified by short silica gel column chromatography (carrier: Chromatorex NH; elution solvent: methylene chloride). The eluted fraction was concentrated. The resulting residue was triturated with ethyl acetate and tert-butyl methyl ether and dried under reduced pressure overnight to obtain 34.28 g of the title compound.

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