Reaction #40740

Reaction equation

diethyl carbonate

1-ethyl-2-naphthalen-1-yl-1H-imidazole

n-BuLi

hexane

→

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

Solvents

Water

THF

Conditions

Workup

1. 1
   workup.STIRRINGThe resulting solution is stirred at −78° C. for 30 min
2. 2
   Temperaturewarmed to rt slowly
3. 3
   workup.STIRRINGstirred for an additional 30 min at rt
4. 4
   Otherto quench
5. 5
   Otherthe reaction, and THF
6. 6
   Otheris evaporated under reduced pressure
7. 7
   ExtractionThe residue is extracted with EtOAc (30 ml×2)
8. 8
   Washthe combined organic layers are washed with water and brine
9. 9
   Dryingdried over sodium sulfate
10. 10
    Concentrationconcentrated
11. 11
    OtherThe crude product is purified through silica gel chromatography (hexanes/EtOAc, from 8:1 to 4:1)

Procedure

To a solution of 1-ethyl-2-naphthalen-1-yl-1H-imidazole (1.11 g, 5 mmol) in anhydrous THF (30 ml) at −78° C. under nitrogen is added a solution of n-BuLi in hexane (1.6 M, 3.44 ml, 5.5 mmol, 1.1 eq.) dropwise. The resulting mixture is stirred at −78° C. for 1 hr, followed by the addition of diethyl carbonate (1.77 g, 15 mmol, 3.0 eq.). The resulting solution is stirred at −78° C. for 30 min, warmed to rt slowly, and stirred for an additional 30 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 8:1 to 4:1) to give 3-ethyl-2-naphthalen-1-yl-3H-imidazole-4-carboxylic acid ethyl ester. LCMS 295 (M+1).

Source