Reacción #607443

Ecuación de reacción

Vilsmeier reagent

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

dichloromethane

Vilsmeier reagent

phosphorus oxychloride

dichloromethane

→

title compound

Rendimiento 81.0%

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

Rendimiento 81.0%

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.ADDITIONAfter the addition
2. 2
   workup.STIRRINGStirring
3. 3
   workup.WAITwas continued for 1.5 h at room temperature
4. 4
   OtroThe 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
   OtroThe phases were separated
7. 7
   Extracciónthe aqueous phase extracted with dichloromethane (2×100 mL)
8. 8
   LavadoThe organic layer was washed with brine (250 mL)
9. 9
   Secadodried over anhydrous Na2SO4
10. 10
    Filtraciónfiltered
11. 11
    OtroThe solvent was removed in vacuo
12. 12
    Otroto give a residue, which
13. 13
    Otrowas 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
    Otrowere collected
16. 16
    Concentraciónconcentrated in vacuo

Procedimiento

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.

Fuente