Реакция #11453

Уравнение реакции

Sodium hydride

phenol

N-[2-(1-benzylpiperidin-4-yl)ethyl]-2-chloro-5,6-dimethyl-3-nitropyridin-4-amine

phenoxide

→

N-[2-(1-benzylpiperidin-4-yl)ethyl]-2,3-dimethyl-5-nitro-6-phenoxypyridin-4-amine

Выход 47.2%

Растворители

diglyme

diglyme

Условия реакции

Обработка

1. 1
   ТемператураThe reaction mixture was heated
2. 2
   Температураat reflux for 1.5 hours
3. 3
   Концентрированиеconcentrated
4. 4
   Другоеto remove the diglyme (60° C. bath, 21 Pa)
5. 5
   ДругоеThe residue was purified by column chromatography
6. 6
   Промывкаeluting first with 1% methanol in dichloromethane
7. 7
   Другоеto remove residual diglyme
8. 8
   Промывкаwith 5% methanol in dichloromethane to elute product
9. 9
   КонцентрированиеThe fractions were concentrated

Методика

Sodium hydride (1.196 g of 60%, 29.9 mmol) was added to a solution of phenol (2.81 g, 29.9 mol) in diglyme (40 mL). The mixture was stirred for 15 minutes after the cessation of gas evolution. A solution of N-[2-(1-benzylpiperidin-4-yl)ethyl]-2-chloro-5,6-dimethyl-3-nitropyridin-4-amine (10.9 g, 27.2 mmol) in hot diglyme was added to the phenoxide mixture. The reaction mixture was heated at reflux for 1.5 hours, cooled to ambient temperature, and then concentrated to remove the diglyme (60° C. bath, 21 Pa). The residue was purified by column chromatography eluting first with 1% methanol in dichloromethane to remove residual diglyme and then with 5% methanol in dichloromethane to elute product. The fractions were concentrated to provide 5.91 g of N-[2-(1-benzylpiperidin-4-yl)ethyl]-2,3-dimethyl-5-nitro-6-phenoxypyridin-4-amine as an orange-brown oil which solidified on standing.

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