Dimethylformamide → 1-Ethyl-2-(naphthalen-1-yl)-1H-imidazole-4-carbaldehyde

HRID 12457Notes

Reaction equation

HRID 12457 reaction equation
Br[C:2]1[N:3]=[C:4]([C:10]2[C:19]3[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=3)[CH:13]=[CH:12][CH:11]=2)[N:5]([CH2:8][CH3:9])[C:6]=1Br.[Li]CCCC.CCCCCC.C[Si](Cl)(C)C.CN([CH:39]=[O:40])C>C1COCC1.CO.O>[CH2:8]([N:5]1[CH:6]=[C:2]([CH:39]=[O:40])[N:3]=[C:4]1[C:10]1[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH:13]=[CH:12][CH:11]=1)[CH3:9]

Participants

9

Reactant 5

HCID 6228DimethylformamideHCID 6397ChlorotrimethylsilaneHCID 8058Hexane2×HCID 534259994,5-Dibromo-1-ethyl-2-(naphthalen-1-yl)-1H-imidazoleHCID 178418339Butyllithium2×

Product 1

HCID 534224531-Ethyl-2-(naphthalen-1-yl)-1H-imidazole-4-carbaldehyde

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

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, followed by dropwise addition of TMSCl (1.188 g, 11 mmol, 1.1 eq.). The resulting solution is stirred at −78° C. After 1 hr, 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 anhydrous DMF (3.65 g, 50 mmol, 5.0 eq.). The resulting solution is stirred at −78° C. for 10 min, and then warmed to rt and stirred for additional 10 min. Water (30 ml) is added to quench the reaction, followed by the addition of MeOH (3 ml). The resulting mixture is stirred at rt for 4 hr. The organic solvent is evaporated under reduced pressure and the residue is extracted with EtOAc (50 ml×3). The combined organic layers are washed with water and brine, and dried over Na2SO4. Concentration and purification through silica gel chromatography (hexanes/EtOAc, from 8:1 to 4:1) affords the title compound. LCMS 251 (M+1).

Workup

  1. stirringThe resulting solution is stirred at −78° C
  2. waitAfter 1 hr
  3. stirringThe resulting mixture is stirred at −78° C. for 1 hr
  4. stirringThe resulting solution is stirred at −78° C. for 10 min
  5. temperaturewarmed to rt
  6. stirringstirred for additional 10 min
  7. customto quench
  8. customthe reaction
  9. stirringThe resulting mixture is stirred at rt for 4 hr
  10. customThe organic solvent is evaporated under reduced pressure
  11. extractionthe residue is extracted with EtOAc (50 ml×3)
  12. washThe combined organic layers are washed with water and brine
  13. dry with materialdried over Na2SO4
  14. concentrationConcentration and purification through silica gel chromatography (hexanes/EtOAc, from 8:1 to 4:1)

Sources & evidence

ORD record
ord-a8f3af09900c4770b3608276e00844f6
Source dataset
uspto-grants-2010_06
Patent number
US07728009B1

Reaction notes

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