Reacción #40742

Ecuación de reacción

dimethyl carbonate

4,5-dichloro-1-ethyl-2-naphthalen-1-yl-1H-imidazole

n-BuLi

hexane

→

5-chloro-3-ethyl-2-naphthalen-1-yl-3H-imidazole-4-carboxylic acid ethyl ester

Disolventes

Water

THF

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.STIRRINGThe resulting solution is stirred at −78° C. for 30 min
2. 2
   Temperaturawarmed to rt slowly
3. 3
   workup.STIRRINGstirred for an additional 60 min at rt
4. 4
   Otroto quench
5. 5
   Otrothe reaction, and THF
6. 6
   Otrois evaporated under reduced pressure
7. 7
   ExtracciónThe residue is extracted with EtOAc (30 ml×2)
8. 8
   Lavadothe combined organic layers are washed with water and brine
9. 9
   Secadodried over sodium sulfate
10. 10
    Concentraciónconcentrated
11. 11
    OtroThe crude product is purified through silica gel chromatography (hexanes/EtOAc, from 20:1 to 10:1)

Procedimiento

To a solution of 4,5-dichloro-1-ethyl-2-naphthalen-1-yl-1H-imidazole (2.87 g, 9.86 mmol) in anhydrous THF (60 ml) at −78° C. under nitrogen is added a solution of n-BuLi in hexane (1.6 M, 6.78 ml, 10.84 mmol, 1.1 eq.) dropwise. The resulting mixture is stirred at −78° C. for 1 hr, followed by the addition of dimethyl carbonate (2.66 g, 29.6 mmol, 3.0 eq.). The resulting solution is stirred at −78° C. for 30 min, warmed to rt slowly, and stirred for an additional 60 min at rt. Water (30 ml) is added to quench the reaction, and THF is evaporated under reduced pressure. The residue is extracted with EtOAc (30 ml×2) and the combined organic layers are washed with water and brine, dried over sodium sulfate, and concentrated. The crude product is purified through silica gel chromatography (hexanes/EtOAc, from 20:1 to 10:1) to give 5-chloro-3-ethyl-2-naphthalen-1-yl-3H-imidazole-4-carboxylic acid ethyl ester. LCMS 315 (M+1).

Fuente