Triethylamine → 8-(2-Chloronicotinoylcarbamoyl)-3-isopropyl-4-methylene-2-oxo-1-oxa-3,8-diazaspiro[4,5]decane

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Reaction Conditions

Reaction Steps

5.8 g of oxalyl chloride are portionwise added to the solution of 6.2 g of 2-chloronicotinic acid amide in 150 ml of anhydrous 1,2-dichloroethane under stirring, then the reaction mixture is heated at 85° C. for 90 minutes. After cooling the mixture to 0° to 5° C. first 12.6 ml of triethylamine and then a solution of 8.4 g of 3-isopropyl-4-methylene-2-oxo-1-oxa-3,8-diazaspiro[4,5]decane in 42 ml of anhydrous 1,2-dichloroethane are portionwise added while maintaining the temperature between 20° and 30° C. The reaction mixture is stirred at room temperature for an additional 30 minutes, then extracted with 200 ml of N sodium hydroxide solution and then with 100 ml of water. After combining the aqueous extract is acidified to a pH value of 5.5 to 6 by adding acetic acid and the mixture is extracted with 1,2-dichloroethane. The organic solution is washed with water, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The residue is recrystallized from ethanol to give the title compound in 54% yield, m.p.: 186°-188° C.

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