Methyl ethyl ketone Ethosuximide

In its manufacture, methyl ethyl ketone is condensed with ethylcyanoacetate to give ethyl-2-cyano-3-methyl-2-pentenoate. That, in turn, adds HCN to give ethyl-2,3-dicyano-3-methyl-pentanoate. Saponification and decarboxylation gives 2-methyl-2-ethyl succinonitrile. Heating with aqueous NH3 gives the diamide which loses NHj and cyclizes to ethosuximide. 

The first report of the preparation of the dialkyl succinimide (29-3) dates back to early in the twentieth cenmry. It is consequently surprising to note that it was introduced as an anticonvulsant, under the name ethosuximide, well after its more recently synthesized congeners. The synthetic route starting from methyl ethyl ketone generally follows that above with the exception of the use of ammonia in the last step. The compound thus differs as well by possessing a somewhat acidic imide proton [30]. 

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