反应 #607443

反应方程式

Vilsmeier reagent

5-bromo-6-(cis-4-isopropylcyclohexoxy)-2-methyl-pyridin-3-amine

dichloromethane

Vilsmeier reagent

phosphorus oxychloride

dichloromethane

→

title compound

收率 81.0%

N′-[5-bromo-6-(cis-4-isopropylcyclohexoxy)-2-methyl-3-pyridyl]-N-ethyl-N-methyl formamidine

收率 81.0%

反应条件

后处理

1. 1
   workup.ADDITIONAfter the addition
2. 2
   workup.STIRRINGStirring
3. 3
   workup.WAITwas continued for 1.5 h at room temperature
4. 4
   其他The reaction mixture was then quenched by the addition of water (100 mL)
5. 5
   workup.ADDITIONthe pH was adjusted to 14 by the addition of a 2.0 molar aqueous NaOH solution (80 mL)
6. 6
   其他The phases were separated
7. 7
   萃取the aqueous phase extracted with dichloromethane (2×100 mL)
8. 8
   洗涤The organic layer was washed with brine (250 mL)
9. 9
   干燥dried over anhydrous Na2SO4
10. 10
    过滤filtered
11. 11
    其他The solvent was removed in vacuo
12. 12
    其他to give a residue, which
13. 13
    其他was purified by column chromatography (silica gel, heptane/ethyl acetate, v/v=1/0-4/1)
14. 14
    workup.ADDITIONFractions containing the pure compound
15. 15
    其他were collected
16. 16
    浓缩concentrated in vacuo

实验过程

The Vilsmeier reagent was freshly prepared by the slow addition of phosphorus oxychloride (7.09 mL, 75.89 mmol, 1.2 eq) to a solution of N,N-ethylmethylformamide (6.61 g, 75.89 mmol, 1.2 eq) in dichloromethane (75 mL) at room temperature. After the addition was complete, the reaction mixture was stirred at room temperature for 1 h. The Vilsmeier reagent was then added drop wise over 40 min to a solution of 5-bromo-6-(cis-4-isopropylcyclohexoxy)-2-methyl-pyridin-3-amine (20.70 g, 63.24 mmol) in dichloromethane (225 mL) at room temperature under inert atmosphere (Ar). Stirring was continued for 1.5 h at room temperature. The reaction mixture was then quenched by the addition of water (100 mL) and the pH was adjusted to 14 by the addition of a 2.0 molar aqueous NaOH solution (80 mL). The phases were separated and the aqueous phase extracted with dichloromethane (2×100 mL). The organic layer was washed with brine (250 mL), dried over anhydrous Na2SO4 and filtered. The solvent was removed in vacuo to give a residue, which was purified by column chromatography (silica gel, heptane/ethyl acetate, v/v=1/0-4/1). Fractions containing the pure compound were collected and concentrated in vacuo to give the title compound (20.23 g, 81%) as a yellow oil.

来源