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

HRID 12464Notes

Reaction equation

HRID 12464 reaction equation
[Cl:1][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]=1Cl.[Li]CC[CH2:23][CH3:24].CCCCCC.[C:31](=O)([O:34]C)[O:32]C>C1COCC1.O>[CH2:23]([O:34][C:31]([C:6]1[N:5]([CH2:8][CH3:9])[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:3][C:2]=1[Cl:1])=[O:32])[CH3:24]

Participants

7

Reactant 4

HCID 8058HexaneHCID 12021Dimethyl CarbonateHCID 59337747HCID 59337747, compoundHCID 178418339Butyllithium

Product 1

HCID 686289415-chloro-3-ethyl-2-naphthalen-1-yl-3H-imidazole-4-carboxylic acid ethyl ester

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

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).

Workup

  1. stirringThe resulting solution is stirred at −78° C. for 30 min
  2. temperaturewarmed to rt slowly
  3. stirringstirred for an additional 60 min at rt
  4. customto quench
  5. customthe reaction, and THF
  6. customis evaporated under reduced pressure
  7. extractionThe residue is extracted with EtOAc (30 ml×2)
  8. washthe combined organic layers are washed with water and brine
  9. dry with materialdried over sodium sulfate
  10. concentrationconcentrated
  11. customThe crude product is purified through silica gel chromatography (hexanes/EtOAc, from 20:1 to 10:1)

Sources & evidence

ORD record
ord-712d0ca79ca34dd384a9ac7acc37c7c0
Source dataset
uspto-grants-2010_06
Patent number
US07728009B1

Reaction notes

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