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

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Reaction Steps

(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.

Provenance & Evidence