Takeda Chemical Industries, Inc.

Haruo Shinbo

Kenzo Naito

Yukio Ishibashi

Kazuo Tsukamura

Disclosed are an advantageous method of industrial production of tert-butyl 3-oxobutylate, which is a useful intermediate for synthesis, characterized by reacting tert-butyl alcohol with diketene in the presence of 4-(tertiary amino) pyridine, and an industrially advantageous method of producing cephalosporin compounds or pharmaceutically acceptable salts thereof, using tert-butyl 3-oxobutylate as an intermediate.

Method for production of T-butyl 3-oxobutyrates and their use

Method for production of t-butyl 3-oxobutyrates and their use

An advantageous method of producing in large amounts on a commercial scale 2-substituted oxyimino-3-oxobutyric acids, which are useful as intermediates in the synthesis of e.g. aminothiazole cephalosporins, is characterized by reacting a tert-butyl 2-substituted oxyimino-3-oxobutyrate with a hydrogen halide in an anhydrous organic solvent.

Method for production of 2-oxyimino-3-oxobutyric acids

An improvement, in per se known method for producing 7-aminocephem compound being important intermediate for producing antimicrobial substances, represented by the formula: ##STR1## wherein R.sup.1 is a hydrogen atom or a methoxy group and R.sup.2 is a residue of a thiol compound, or a salt or ester thereof, by reacting a compound of the formula: ##STR2## wherein R.sup.1 is as defined above and R is a carboxylic acid acyl group, or a salt or ester thereof, with a thiol compound or a salt thereof, is characterized in that the reaction is conducted in an organic solvent in the presence of a dihalophosphoric acid to give the compound [II] in high yield and high purity.

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Hyogo, Japan

Haruo Shinbo