Methyl iodide → 2-benzyloxymethyl-5-(3,5-dichlorophenylthio)-4-isopropyl-1-methyl-1H-imidazole

HRID 1415992Notes

Reaction equation

HRID 1415992 reaction equation
[CH2:1]([O:8][CH2:9][C:10]1[NH:11][C:12]([S:18][C:19]2[CH:24]=[C:23]([Cl:25])[CH:22]=[C:21]([Cl:26])[CH:20]=2)=[C:13]([CH:15]([CH3:17])[CH3:16])[N:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:27]I.[OH-].[Na+]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.O1CCCC1>[CH2:1]([O:8][CH2:9][C:10]1[N:11]([CH3:27])[C:12]([S:18][C:19]2[CH:24]=[C:23]([Cl:25])[CH:22]=[C:21]([Cl:26])[CH:20]=2)=[C:13]([CH:15]([CH3:17])[CH3:16])[N:14]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 14798Sodium HydroxideHCID 1784190342-Benzyloxymethyl-5-(3,5-dichlorophenylthio)-4-isopropyl-1H-imidazole

Product 1

HCID 221305032-benzyloxymethyl-5-(3,5-dichlorophenylthio)-4-isopropyl-1-methyl-1H-imidazoleYield 67%

Reagents, catalysts & solvents 2

HCID 74236Tetrabutylammonium BromideCatalystHCID 8028TetrahydrofuranSolvent

Procedure

(4)In 50 ml of dry tetrahydrofuran was dissolved 15 g (44 mmol)of 2-benzyloxymethyl-5-(3,5-dichlorophenylthio)-4-isopropyl-1H-imidazole (16a). To this solution was added 6.87 g (48.4 mmol)of methyl iodide under ice-cooling, further followed by addition of 1.94 g (48.4 mmol)of sodium hydroxide and 100 mg of tetrabutylammonium bromide. After the ice-water bath was removed, the mixture was stirred for 1 hour. This reaction mixture was concentrated under reduced pressure and the residue was neutralized with hydrochloric acid and sodium hydrogen carbonate to be weakly basic and extracted twice with ethyl acetate. The pooled organic layer was washed with water and dried over sodium sulfate. The solvent was then distilled off under reduced pressure and the residue was fractionated by silica gel chromatography (3% ethyl acetate in methylene chloride). From the first fraction, 3.5 g (yield 22%)of the objective position isomer (17a')was obtained as oil. From the subsequent fraction, 10.4 g (yield 67%)of the objective 2-benzyloxymethyl-5-(3,5-dichlorophenylthio)-4-isopropyl-1-methyl-1H-imidazole (17a) was obtained as oil.

Workup

  1. temperaturecooling
  2. customAfter the ice-water bath was removed
  3. concentrationThis reaction mixture was concentrated under reduced pressure
  4. extractionextracted twice with ethyl acetate
  5. washThe pooled organic layer was washed with water
  6. dry with materialdried over sodium sulfate
  7. distillationThe solvent was then distilled off under reduced pressure
  8. customFrom the first fraction, 3.5 g (yield 22%)of the objective position isomer (17a')was obtained as oil

Sources & evidence

ORD record
ord-7cbd843cf3af4c5eb3d496bff613e48c
Source dataset
uspto-grants-1999_06
Patent number
US05910506

Reaction notes

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