Toshin Chemical Co., Ltd.

Kenichi Ishibashi

Susumu Ishiguro

Fumitake Shimada

Reiko Komaki

Toshio Itoh

A novel and efficient method is proposed for the preparation of isosorbide-5-nitrate which is a promising medicinal compound for several diseases due to disorder in heart. The method comprises direct nitration of isosorbide with a concentrated nitric acid in a specific reaction medium containing an aromatic hydrocarbon solvent, e.g. benzene, in addition to conventional acetic acid and acetic anhydride. After neutralization of the reaction mixture and removal of the dinitrate as a byproduct therefrom, the reaction mixture is admixed with an aqueous solution of sodium hydroxide so that a sodium salt of isosorbide-5-nitrate is precipitated in the form of a hydrate, which is a novel compound not known in the prior art. This hydrate sodium salt is then decomposed with an acid to give the desired isosorbide-5-nitrate in a high yield.

Method for the preparation of isosorbide-5-nitrate and sodium

A novel and very elegant method is proposed for the preparation of N.sub.1 -(2-tetrahydrofuryl)-5-substituted or -unsubstituted uracil, especially, N.sub.1 -(2-tetrahydrofuryl)-5-fluorouracil, by the reaction of the corresponding 5-substituted uracil compound with 2,3-dihydrofuran. The reaction is performed in the presence of a chlorosilane compound, e.g. dimethyldichlorosilane, and a catalytic amount of an organic amine compound and can proceed very rapidly without disadvantageous side reactions to give the objective compound with high purity in a high yield.

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Urawa, Japan

Kenichi Ishibashi