Reaktion #11453

Reaktionsgleichung

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

Ausbeute 47.2%

Lösungsmittel

diglyme

diglyme

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturThe reaction mixture was heated
2. 2
   Temperaturat reflux for 1.5 hours
3. 3
   Einengenconcentrated
4. 4
   Sonstigeto remove the diglyme (60° C. bath, 21 Pa)
5. 5
   SonstigeThe residue was purified by column chromatography
6. 6
   Wascheneluting first with 1% methanol in dichloromethane
7. 7
   Sonstigeto remove residual diglyme
8. 8
   Waschenwith 5% methanol in dichloromethane to elute product
9. 9
   EinengenThe fractions were concentrated

Vorschrift

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.

Quelle