Hydrochloric Acid → 2-(tert-Butyldimethylsilyl)-N,N-dimethyl-1H-imidazole-1-sulfonamide

HRID 1760464Notes

Reaction equation

HRID 1760464 reaction equation
[CH3:1][N:2]([CH3:20])[S:3]([N:6]1[C:10](C=O)=[CH:9][N:8]=[C:7]1[Si:13]([C:16]([CH3:19])([CH3:18])[CH3:17])([CH3:15])[CH3:14])(=[O:5])=[O:4].Cl.[OH-].[Na+]>>[CH3:1][N:2]([CH3:20])[S:3]([N:6]1[CH:10]=[CH:9][N:8]=[C:7]1[Si:13]([C:16]([CH3:18])([CH3:17])[CH3:19])([CH3:15])[CH3:14])(=[O:4])=[O:5]

Participants

4

Reactant 3

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 99959681-Dimethylsulfamoyl-2-t-butyldimethylsilyl-5-imidazolecarboxaldehyde

Product 1

HCID 64202092-(tert-Butyldimethylsilyl)-N,N-dimethyl-1H-imidazole-1-sulfonamide

Procedure

1-(N,N-dimethylsulfamoyl)imidazole (1.5 g, 8.6 mmol) was taken up in 28 mL of THF. The solution was cooled to −78° C. and n-BuLi (5.4 mL, 8.6 mmol) added dropwise via syringe. After stirring at −78° C. for 1 h TBSCl (1.3 g, 8.56 mmol) in 10 mL of THF was added. The bath was removed and the reaction allowed to warm-up to rt. The reaction mixture was stirred overnight. The reaction mixture was cooled to −20° C. and n-BuLi (5.4 mL, 8.6 mmol) added. After 45 min phenyldisulfide (1.9 g, 8.6 mmol) in 8 mL of THF was added. The reaction mixture was stirred at rt for 48 h. The reaction mixture was quenched with saturated ammonium chloride and extracted with ethyl acetate. The organic layer was collected and washed with water and then brine. The solution was dried over sodium sulfate and the solvent removed under reduced pressure. Flash chromatography (2.5% EtOAc/hexane) afforded 2.8 g (7.0 mmol) of 2-(t-butyldimethylsilyl)-5-phenylsulfanylimidazole-1-sulfonic acid dimethylamide (1) as a yellow color oil. The compound (1) (2.8 g, 7.0 mmol) was dissolved in THF and the solution cooled to 0° C. TBAF (7.0 mL, 7.0 mmol) was added dropwise to the solution. The reaction mixture was stirred overnight at rt. The next day the reaction was quenched with water and extracted with ethyl acetate. The organic layer was washed with water followed by brine. The solution was dried over sodium sulfate and the solvent removed under reduced pressure. Flash chromatography (50% EtOAc/hexane) afforded 474 mg of 5-phenylsulfanylimidazole-1-sulfonic acid dimethylamide (2) and 290 mg of 5-phenylsulfanyl-1H-imidazole (3) (H). The 478 mg of (2) was added to 2N HCl and the solution heated at reflux for 2 h. The reaction mixture was made basic with 2N NaOH and extracted with ethyl acetate. The organic layer was washed with water followed by brine. The solution was dried over sodium sulfate and the solvent removed under reduced pressure. Flash chromatography (EtOAc) afforded (3) as a white crystalline solid. A combined total of 360 mg (2.0 mmol) of (3) is recovered.

Workup

  1. temperaturethe solution heated
  2. temperatureat reflux for 2 h
  3. extractionextracted with ethyl acetate
  4. washThe organic layer was washed with water
  5. dry with materialThe solution was dried over sodium sulfate
  6. customthe solvent removed under reduced pressure

Sources & evidence

ORD record
ord-e7ee15bf7adc4cff9e5fe76e39c9e5b6
Source dataset
uspto-grants-2005_01
Patent number
US06841684B2

Reaction notes

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