Water → HCID 12790771, compound

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Reaction Steps

In a three-necked flask, fitted with stirrer, reflux condenser and gas inlet tube, 44 g of sodium hydroxide (1.1 mol) and 50 ml of water are introduced. While passing nitrogen through the flask, the solution is cooled to 45° and then 11.6 g of (1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethanol (0.045 mol) [prepared by the method of J. Med. Chem. 12, 784, (1969)], 0.75 g of benzyltrimethylammonium chloride and 150 ml of tetrahydrofuran are added. To the mixture, which is warmed to 50°, 8.3 g of 4-chloromethyl-2-methylthiazole, hydrochloride (0.045 mol) are added and the mixture is stirred vigorously for two hours at 60°. The filtered biphasic solution is transferred into a separating funnel, the lower aqueous sodium hydroxide is extracted with 10 ml of tetrahydrofuran. The combined tetrahydrofuran layers are treated with charcoal and after drying with sodium sulphate, the solvent is evaporated in vacuo. The resulting oily product, dissolved in 250 ml of ether, is allowed to stand overnight in a refrigerator, by which operation unreacted 1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethanol is separated. Filtering off and addition of ethereal hydrochloric acid to the clear ethereal solution yields the hydrochloride of 4-[[1-(2,4-dichlorophenyl)-2-(1H-imidazol-1-yl)ethoxy]methyl]-2-methylthiazole. Yield: 12.8 g (71%). Recrystallization from acetonitrile gives a hydrochloride with the m.p. of 194°-196° C.

Provenance & Evidence