Reaction #40737

Reaction equation

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

n-BuLi

hexane

n-BuLi

hexane

chlorotrimethylsilane

diethyl carbonate

tetrabutylammonium fluoride

→

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

Solvents

THF

THF

Water

THF

Conditions

Workup

1. 1
   workup.STIRRINGThe resulting solution is stirred at −78° C
2. 2
   workup.WAITAfter 1 hour
3. 3
   workup.STIRRINGThe resulting mixture is stirred at −78° C. for 1 hr
4. 4
   workup.STIRRINGThe resulting solution is stirred at −78° C. for 30 min
5. 5
   Otherwaned to rt
6. 6
   workup.STIRRINGstirred for an additional 30 min at rt
7. 7
   Otherto quench
8. 8
   Otherthe reaction, and THF
9. 9
   Otheris evaporated under reduced pressure
10. 10
    ExtractionThe residue is extracted with EtOAc (30 ml×2)
11. 11
    WashThe combined organic layers are washed with water and brine
12. 12
    Dryingdried over sodium sulfate
13. 13
    Concentrationconcentrated
14. 14
    Otherto give the crude product, which
15. 15
    workup.STIRRINGthe resulting mixture is stirred at it for 2 hr
16. 16
    OtherThe solvent is evaporated under reduced pressure
17. 17
    workup.ADDITIONthe residue is diluted with water (30 ml)
18. 18
    ExtractionThe mixture is extracted with EtOAc (30 ml×3)
19. 19
    Washwashed with water and brine
20. 20
    Dryingdried over Na2SO4
21. 21
    Concentrationconcentrated
22. 22
    OtherPurification through silica gel chromatography (hexanes/EtOAc, from 8:1 to 4:1)

Procedure

To a solution of 4,5-dibromo-1-ethyl-2-naphthalen-1-yl-1H-imidazole (3.80 g, 10 mmol) in anhydrous THF (60 ml) at −78° C. under nitrogen is added a solution of n-BuLi in hexane (1.6 M, 6.88 ml, 11 mmol, 1.1 eq.) dropwise. The resulting mixture is stirred at −78° C. for 1 hr, after which chlorotrimethylsilane (1.188 g, 11 mmol, 1.1 eq.) is added. The resulting solution is stirred at −78° C. After 1 hour, n-BuLi in hexane (1.6 M, 6.88 ml, 11 mmol, 1.1 eq.) is added dropwise. The resulting mixture is stirred at −78° C. for 1 hr, followed by the addition of diethyl carbonate (3.54 g, 30 mol, 3.0 eq.). The resulting solution is stirred at −78° C. for 30 min, waned 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). The combined organic layers are washed with water and brine, dried over sodium sulfate, and concentrated to give the crude product, which is dissolved in THF (30 ml). To this THF solution is added tetrabutylammonium fluoride (1.1 eq.), and the resulting mixture is stirred at it for 2 hr. The solvent is evaporated under reduced pressure, and the residue is diluted with water (30 ml). The mixture is extracted with EtOAc (30 ml×3), washed with water and brine, dried over Na2SO4 and concentrated. Purification through silica gel chromatography (hexanes/EtOAc, from 8:1 to 4:1) affords 1-ethyl-2-naphthalen-1-yl-1H-imidazole-4-carboxylic acid ethyl ester. LCMS 295 (M+1).

Source