Takeda Chemical Industries, Inc.

Lederle (japan), Ltd.

Kazuo Tsukamura

Kenzo Naito

Masayasu Kato

Haruo Shinbo

Sakae Aoyagi

Haruo Sinbo

A novel method of producing a cephalosporin compound of the formula ##STR1## wherein R.sup.1 is a hydrogen atom or an acyl group; R is a hydrogen atom or an ester residue; the dotted line means a double bond in 2- or 3-position of the cephem ring; and R.sup.4 is a nucleophilic compound residue, or a salt thereof, directedly in one step from a compound of the formula ##STR2## wherein R.sup.1, R and the dotted line have the meanings defined above, or a salt thereof, by reacting in the presence of an organic solvent the compound [II] or a salt thereof, a nucleophilic compound or a salt thereof, and (1) a trivalent or pentavalent cyclic phosphorus compound having a partial structure of the formula ##STR3## wherein W is an oxygen atom, a sulfur atom or NR.sup.2 ; W.sup.1 is an oxygen atom, a sulfur atom or NR.sup.3 ; and R.sup.2 and R.sup.3 may be the same or different and each means a hydrogen atom or a hydrocarbon group, or a salt thereof, or (2) a reaction product of a compound having a partial structure of the formula ##STR4## wherein W and W.sup.1 have the same meaning as defined above, or a salt thereof, with a phosphorus oxyhalide, trihalide or pentahalide.

Method for production of cephalosporin compounds

Novel crystals of sodium 7.beta.-[2-(2-aminothiazol-4-yl)-(Z)-2-methoxyiminoacetamido]-3-[(1,2,3-th iadiazol-5-yl)thiomethyl] ceph-3-em-4-carboxylate showing characteristic peaks at interplanar spacings (d) of 9.3, 8.9, 5.3, 5.1, 4.4, 4.3 and 3.8 .ANG. in the powder X-ray diffraction pattern which are very stable and do not easily cause discoloration and decomposition.

Crystals of sodium cephemcarboxylate

A method is provided for producing a 1,3,2-dioxaphosphole of the formula ##STR1## wherein ##STR2## respresents a benzene ring which may be substituted and R represents an aryl, alkoxy or aralkyloxy group which may be substituted, which comprises reacting a catechol compound of the formula ##STR3## wherein ##STR4## is an defined above, with a compound of the formula ##STR5## wherein X is a halogen atom and R is as defined above, at a temperature not higher than about 30.degree. C. in the presence of a base.

Method for production of 1,3,2-dioxaphospholes

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.

Method for producing 7-aminocephem compounds

A solid cephalosporin derivative having the formula: ##STR1## wherein X is chlorine or bromine, n is a number from zero to 6, is found to have high stability in storage and may be used as an active component of an antimicrobial composition.

Growing community of inventors

Hyogo, Japan

Kazuo Tsukamura