Diethyl Ether → HCID 22612692, compound

Participants

Reaction Steps

At 0° C., a solution of 1.5 g (3.6 mmol) of 4-(4′-trifluoromethoxy-4-biphenylyl)-2-(2,6-difluorophenyl)-4,5-dihydro-1H-imidazole (for example from Example V-1) in 15 ml of dichloromethane was admixed first with 0.75 ml (0.55 g; 5.4 mmol) of triethylamine and then with 4 ml (0.41 g; 4.32 mmol) of chloromethyl ethyl ether. After the mixture had been stirred overnight, approximately 50% of starting material were still present (TLC). A further 0.25 ml of triethylamine and 0.17 ml of the ether were introduced. Since no further reaction could be detected, another 0.25 ml of triethylamine was added and the mixture was heated to the boil. For work-up, the reaction mixture was extracted with 10% strength citric acid and 1N aqueous sodium hydroxide solution, dried, concentrated and chromatographed over a silica gel column (Ø=3 cm, 1=30 cm). Elution with cyclohexane/ethyl acetate using a 5-stage gradient from 20:1 to 3:1 gave, as second fraction, 0.30 g (17% of theory) of 1-ethoxymethyl-4-(4′-trifluoromethoxy-4-biphenylyl)-2-(2,6-difluorophenyl)-4,5-di-hydro-1H-imidazole (I-6a) and, as third fraction, 0.34 g (20% of theory) of 3-ethoxymethyl-4-(4′-trifluoromethoxy-4-biphenylyl)-2-(2,6-difluorophenyl)-4,5-di-hydro-3H-imidazole (I-6b).

Provenance & Evidence