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ChemicalBook CAS DataBase List ETHOSUXIMIDE
77-67-8

ETHOSUXIMIDE synthesis

4synthesis methods
Ethosuximide, 3-ethyl-3-methypyrrolidine-2,5-dione (9.3.4) is synthesized from methylethylketone and cyanoacetic ester, which are condensed in Knoevanagel reaction conditions. Then hydrogen cyanide is added to the resulting product (9.3.1). After acidic hydrolysis and decarboxylation of synthesized dinitrile (9.3.2), 2-methyl-2-ethylsuccinic acid (9.3.3) is formed. Reacting this product with ammonia gives the diammonium salt, and heterocyclization into the ethosuximide (9.3.4) takes place during subsequent heating [8,9].

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Yield:-

Steps:

Multi-step reaction with 3 steps
1: 58 percent / Raney nickel (W-2) / ethanol / 3 h / Heating
2: 56 percent / pyridinium chlorochromate / CH2Cl2 / 2 h / Ambient temperature
3: 47 percent / cerium(IV) ammonium nitrate / acetonitrile; H2O / 1 h / Ambient temperature

References:

Ishibashi, Hiroyuki;Nakaharu, Tohru;Nishimura, Masako;Nishikawa, Atsuko;Kameoka, Chisato;Ikeda, Masazumi [Tetrahedron,1995,vol. 51,# 10,p. 2929 - 2938]

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