Formic Acid → N,N'-Dicyclohexylurea

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Reaction Steps

In this example, 11.7 g (0.2534 mole) of formic acid was added to a stirred slurry containing 26.1 (0.1267 mole) of dicyclohexyl carbodiimide in 300 ml of methylene chloride at about -10° C. A precipitate of dicyclohexyl urea formed. The mixture was then stirred at 0° to 3° C. for 20 minutes and then a solution containing 24.6 g (0.0756 mole) of N-(2-[4-(4-trifluoromethylphenoxy)-phenoxy]propyl)-N-methylformamide and 0.1267 mole of 4-dimethylaminopyridine in 125 ml of methylene chloride was slowly added over a 2-hour period. The mixture was allowed to warm to room temperature and stirred at room temperature overnight (about 12 hours). Thin layer chromatographic analysis of a sample showed complete reaction. The mixture was then filtered and the filter cake washed with methylene chloride. The combined filtrate and washing was washed with 200 ml aqueous 5% by weight hydrochloric acid, then with 200 ml of water and then dried over magnesium sulfate and filtered. The filtrate was evaporated under vacuum affording a semi-oil product. The semi-oil product was treated with ethyl ether and then filtered. The filtrate was evaporated under vacuum affording an oil which was then chromatographed on 300 g of silica gel sequentially eluting with pet (i.e., petroleum ether); 80:20 volume pet:ethyl ether; 60:40 volume pet:ethyl ether; ethyl ether and 96% ethyl ether in methanol affording the title compound as an oil contaminated with water and methanol. The oil was then dissolved in methylene chloride and the resulting solution then washed with water, then with 100 ml of a saturated aqueous solution of sodium bicarbonate and then dried over magnesium sulfate and filtered. The filtrate was evaporated under vacuum affording 10.3 g of the title compound as a clear oil. Elemental analysis: Calculated: C-61.19%, H-5.13%, N-3.96%; Found: C-62.56%, H-5.31%, N-4.05%.

Provenance & Evidence