2-Chloro-1-ethyl-1H-imidazole synthesis

Yield:-

Reaction Conditions:

Stage #1: N-Ethylimidazolewith n-butyllithium in tetrahydrofuran;hexane at -78; for 0.5 h;
Stage #2: hexachloroethane in tetrahydrofuran;hexane at -78; for 1 h;

Steps:

5.1

(1) 2-Chloro-1-ethyl-1H-imidazole To a solution of 1-ethyl-1H-imidazole (2.2 g) in THF (12 ml), n-BuLi (9.1 ml, 2.64 N in hexane) was added dropwise at -78°C under an argon atmosphere. After stirring at the same temperature for 30 minutes, a solution of hexachloroethane (5.7 g) in THF (12 ml) was added dropwise and stirred at the same temperature for 1 hour. The reaction mixture was diluted with saturated aqueous ammonium chloride, warmed to room temperature, and extracted with AcOEt. After washing with water and saturated aqueous sodium chloride, the organic layer was dried over MgSO₄, filtered and then evaporated under reduced pressure to remove the solvent. The resulting crude product was purified by column chromatography (OH-type SiO₂, AcOEt/hexane = 0% to 20%) to give the titled compound (2.74 g, colorless oil). ¹H NMR (600 MHz, CDCl₃) δ ppm: 1.40 (t, J=7.3 Hz, 3H), 3.96 (q, J=7.3 Hz, 2H), 6.88-6.98 (m, 2H)

References:

EP1988081,2008,A1 Location in patent:Page/Page column 36