Diethyl acetamidomalonate (CAS NO.: ), which is also known as , acetamido-, diethyl ester, could be produced through the following synthetic routes.

A. Diethyl isonitrosomalonate (CAS NO.: ). In a 500-ml. three-necked, round-bottomed flask, equipped with a mechanical stirrer and thermometer, is placed 50 g. (47.4 ml., 0.312 mole) of diethyl malonate. The flask is cooled in an ice bath, and a mixture of 57 ml. of glacial acetic acid and 81 ml. of water is added with stirring. With the temperature at about 5°, a total of 65 g. of sodium nitrite (0.944 mole) is added in portions over a period of 1.5 hours, the temperature being maintained around 5° during the addition. After all the sodium nitrite is added, the ice bath is removed, and the stirring is continued for 4 hours. During this time, the temperature reaches a maximum of 34–38° within 2 hours and falls to about 29° by the end of the stirring period. Gases which escape during the reaction (mostly oxides of nitrogen) are led to the hood.

The reaction mixture is transferred to a 300-ml. separatory funnel and is extracted with two 50-ml. portions of ether. The combined ethereal solution of diethyl isonitrosomalonate is used in the next step immediately or, if desired, may be used after storage in a refrigerator overnight.

B. Diethyl acetamidomalonate (CAS NO.: ). The solution of diethyl isonitrosomalonate described above, 86 g. (0.842 mole) of acetic anhydride, and 225 ml. (3.95 moles) of glacial acetic acid are placed in a 1-l., three-necked, round-bottomed flask fitted with a mechanical stirrer, a thermometer, and a dropping funnel. With vigorous stirring 78.5 g. (1.20 moles) of zinc dust is added in small portions over a period of 1.5 hours in such a manner that the temperature of the reaction is maintained at 40–50°. The reaction is markedly exothermic during most of the zinc addition, and intermittent cooling (water bath) is required. After all the metal has been added, the mixture is stirred for an additional 30 minutes.

The reaction mixture is filtered with suction and the cake is washed thoroughly with two 200-ml. portions of glacial acetic acid. The combined filtrate and washings are evaporated under reduced pressure on the steam bath until a thick oil, which generally partially crystallizes, remains. To purify the crude product, 100 ml. of water is added, and the flask is warmed on a steam bath until the solid melts. The mixture of water and oil is stirred rapidly in an ice bath, and diethyl acetamidomalonate crystallizes as a fine white product. After cooling in an ice bath for an additional hour, the product is collected by filtration, washed once with cold water, and dried in air at 50°. A second crop is obtained by concentrating the mother liquor under reduced pressure. The yield of diethyl acetamidomalonate, m.p. 95–97°, is 52–53 g. (77–78%) based on malonic ester.