反应详情

1-(3,5-Difluorobenzyl)-2-mercaptoimidazole (2.26 g, 0.010) and potassium hydroxide (0.056 g, 0.010 mole) are dissolved in dimethylformamide (10 ml) containing water (0.5 ml) with stirring under argon at ambient temperature. To this solution is added dropwise 2-dimethylaminoethyl chloride (1.08 g, 0.010 mole) in toluene (10 ml). [This solution is prepared by stirring 1.44 g of dimethylaminoethyl chloride hydrochloride with an excess of sodium hydroxide pellets in the presence of toluene (10 ml) and a few drops of water, followed by filtering the solution of neutralized base.] The reaction mixture is warmed to 95° C., stirred at this temperature for one hour, cooled and then diluted with water. The layers are shaken together and separated and then the aqueous phase is extracted twice with ether. The toluene and ether extracts are combined and the solvents are removed in vacuo. The residual oil is dissolved in ether and hydrogen chloride in ether is added slowly with stirring until a slight excess is present. The precipitated white crystalline solid is filtered and recrystallized from ethanol ether to give 2-(2-dimethylaminoethylthio)-1-(3,5-difluorobenzyl)imidazole dihydrochloride.

1. custom[This solution is prepared
2. filtrationby filtering the solution of neutralized base
3. temperature] The reaction mixture is warmed to 95° C.
4. stirringstirred at this temperature for one hour
5. temperaturecooled
6. additiondiluted with water
7. stirringThe layers are shaken together
8. customseparated
9. extractionthe aqueous phase is extracted twice with ether
10. customthe solvents are removed in vacuo
11. dissolutionThe residual oil is dissolved in ether
12. additionhydrogen chloride in ether is added slowly
13. stirringwith stirring until a slight
14. filtrationThe precipitated white crystalline solid is filtered
15. customrecrystallized from ethanol ether