Tetrahydrofuran → 4-(3-Trifluoromethyl-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole

HRID 419730Notes

Reaction equation

HRID 419730 reaction equation
O1CCCC1.[F:6][C:7]([F:20])([F:19])[C:8]1[CH:9]=[C:10]([C:14]2[N:15]=[CH:16][NH:17][CH:18]=2)[CH:11]=[CH:12][CH:13]=1.[H-].[Na+].[CH3:23][Si:24]([CH3:31])([CH3:30])[CH2:25][CH2:26][O:27][CH2:28]Cl>O>[F:20][C:7]([F:6])([F:19])[C:8]1[CH:9]=[C:10]([C:14]2[N:15]=[CH:16][N:17]([CH2:28][O:27][CH2:26][CH2:25][Si:24]([CH3:31])([CH3:30])[CH3:23])[CH:18]=2)[CH:11]=[CH:12][CH:13]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 24758Sodium hydrideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 178506151HCID 178506151, compound

Product 1

HCID 121144924-(3-Trifluoromethyl-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazoleYield 69.8%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
0 °C

Procedure

To a 250 mL round bottom flask (fitted with rubber septum and nitrogen blanket and stir bar) add Tetrahydrofuran (30 mL; 368.66 mmoles; 30.00 mL; 26.58 g), 4-(3-Trifluoromethyl-phenyl)-1H-imidazole (1.047 g; 1.00 equiv; 4.93 mmoles; 1.05 g) and cool the mixture to 0° C. with stirring on and hold for 5 min. Add sodium hydride (0.138 g; 1.11 equiv; 5.46 mmoles; 138.00 mg) to the flask and stir the reaction for 20 min. Add 2-(trimethylsilyl)ethoxymethyl chloride (1.15 mL; 1.31 equiv; 6.49 mmoles; 1.15 mL; 1.08 g) and allow the reaction to warm to room temperature. Dilute the reaction with water and extract the mixture two times with ethyl acetate and discard the aqueous phase. Dry the material over Na2SO4, filter, and concentrate to dryness. Purify the crude mixture by flash chromatography on silica gel eluting with ethyl acetate/hexane from 10-60% EtOAc. Combine the appropriate fractions and concentrated to give 4-(3-Trifluoromethyl-phenyl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole (1.178 g; 0.70 equiv; 3.44 mmoles; 1.18 g; 69.71% yield).

Workup

  1. customTo a 250 mL round bottom flask (fitted with rubber septum and nitrogen blanket and stir bar)
  2. customthe reaction for 20 min
  3. customthe reaction
  4. temperatureto warm to room temperature
  5. additionDilute
  6. extractionextract the mixture two times with ethyl acetate
  7. dry with materialDry the material over Na2SO4
  8. filtrationfilter
  9. concentrationconcentrate to dryness
  10. customPurify the crude mixture by flash chromatography on silica gel eluting with ethyl acetate/hexane from 10-60% EtOAc
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-2d58971e79754bc5a35e0eba554a09ae
Source dataset
uspto-grants-2012_01
Patent number
US08093383B2

Reaction notes

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