反应详情

To a mixture of imidazole (4.5 g, 65.8 mM) and sodium hydride (50% by weight in mineral oil, 3.15 g, 66 mM) at 50° C. was added 4-(2-bromoethyl)-1-piperidine carboxaldehyde (12 g, 55 mM) and the reaction was heated at 50° C. for 3 hrs. The solvent was removed in vacuo and water (about 100 ml) was added to the residue and then the mixture was extracted with methylene chloride (3×100 ml). The combined extracts, dried over Na2SO4, were stripped to dryness and purified on silica gel columns, eluted with methanol-methylene chloride (1:9 parts by volume) to give an oil (10.4 g) which was then refluxed with 2 N hydrochloric acid (55 ml) in dioxane (400 ml) for 5 hrs. The solvent was removed and the product was crystallized from ethanol diethyl ether yield 4-[2-(1H-imidaz-1-yl)ethyl]piperidine-hydrate-dihydrochloride in overall yield of 55 %. 8.2 g of 4-[2-(1H-imidaz-1-yl)ethyl]piperidine-hydrate-dihydrochloride was converted to free base by dissolving in water (100 ml) at pH 11 and extracting with methylene chloride. Evaporation of the methylene chloride extracts in vacuo gave 5.1 g of free base.

1. extractionextracting with methylene chloride
2. customEvaporation of the methylene chloride