Ethyl 4-(1-hydroxy-1-methylethyl)-2-propyl-imidazole-5-carboxylate

Pale Yellow Solid

An Olmesartan (O550000) intermediate.

Ethyl 4-(1-hydroxy-1-methylethyl)-2-propyl-imidazole-5-carboxylate is a synthetic drug with pharmacological properties that are similar to those of the natural product medoxomil. It has been shown to be a potent blocker of the GABA receptor and is used for the treatment of epilepsy.It has been shown to be an inhibitor of rat liver microsomes and also has a high affinity for the enzyme cilexetil, which is responsible for the conversion of cilexetil into its active form.

To a solution of MeMgCl(55.86 g, 0.74 mol) in tetrahydrofuran was added a solution of diethyl 2-propyl imidazole- 4,5-dicarboxylate (50 g,0.19 mol) in tetrahydrofuran (200 ml) at -10 to 0°C under N2 atmosphere. The mixture was stirred at -5 to 0°C for 10 minutes. The reaction mass was quenched into 400 ml 25 % ammonium chloride solution, followed by extraction with ethyl acetate (300 ml). The organic phase was separated, washed with brine, dried over Na2SO4, and concentrated in vacuo to give Ethyl 4-(1-hydroxy-1-methylethyl)-2-propyl-imidazole-5-carboxylate, which was crystallized using diisopropyl ether. Yield: 85-90 %.

Ethyl 4-(1-hydroxy-1-methylethyl)-2-propyl-imidazole-5-carboxylate is a crucial intermediate for the synthesis of olmesartan medoxomil, which can be produced via the reaction of diethyl 2-propyl-imidazole-4,5-dicarboxylate, the raw material, with methylmagnesium bromide, followed by the acidification with saturated ammonium chloride solution.

Ethyl 4-(1-hydroxy-1-methylethyl)-2-propyl-imidazole-5-carboxylate is sensitive to the skin and may cause allergic skin reactions. It is irritating to the skin and eyes and may also cause respiratory irritation. It is poisonous to aquatic organisms.