Process for preparing 3-substituted-methyl-3-cephem derivatives
AssigneeYamanouchi Pharmacutical Co., Ltd.
InventorsTadao Shibanuma, Kohji Nakano, Noriaki Nagano, Yukiyasu Murakami, Ryuichiro Hara, Akio Koda, Atsuki Yamazaki
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Abstract
Various 7-amino-3-substituted-methyl-3-cephem-4-carboxylic acids and lower alkylsilyl derivatives such as 7-amino-3-(2,3-cyclopenteno-1-pyridiniomethyl)-3-cephem-4-carboxylic acid iodide and trimethylsilyl 7-trimethyl-silylamino-3-(5,6,7,8-tetrahydro-2-isoquinoliniomethyl)-3-ceph em-4-carboxylate iodide are valuable intermediates in the preparation of new and novel antibacterial agents. A new process for the preparation of these acids and the derivatives has been devised.
Claims6
A process for the preparation of 7-amino-3-substituted-methyl-3-cephem-4-carboxylic acid or carboxylate represented by the general formula (I.sub.2)
- wherein --.sup..sym. A represents ##STR32## wherein R.sup.2 is a hydrogen atom or an amino group, and n is an integer of 1 to 2;
- Y.sup.- represents an anion selected from the group consisting of halogen, sulfonate, benzenesulfonate, acetate, fumarate and citrate anions, which comprises reacting, in an inert, organic solvent and at a temperature of from about -20.degree. to about 40.degree. C., 7-amino-3-halogenomethyl-3-cephem-4-carboxylic acid of the formula (II) ##STR33## wherein X is a halogen atom selected from the group consisting of chlorine, bromine, iodine and fluorine, with (tri-lower-alkylsilyl)trifluoroacetamide of the formula ##STR34## wherein R.sup.1 is a lower alkyl group and a pyridine compound of the formula (IV) ##STR35## and then releasing the tri-loweralkylsilyl protective groups of the formed compound of the formula ##STR36##
A process for the preparation of tri-lower-alkylsilyl derivatives represented by the general formula ##STR37## wherein --.sup..sym. A represents ##STR38## wherein R.sup.2 is a hydrogen atom or an amine group, and n is an integer of 1 to 2;
- Y.sup..crclbar. represents an anion selected from the group consisting of halogen, sulfonate, benzenesulfonate, and citrate anions;
- and
- R.sup.1 represents a lower alkyl group;
- which comprises reacting, in an inert organic solvent and at a temperature of from about -20.degree. to about 40.degree. C., 7-amino-3-halogenomethyl-3-cephem-4-carboxylic acid of the formula ##STR39## wherein X is a halogen atom selected from the group consisting of chlorine, bromine, iodine and fluorine, with a (tri-loweralkylsilyl)trifluoroacetamide of the formula ##STR40## and a pyridine compound of the formula (IV) ##STR41##
A process for the preparation of 7-amino-3-substituted methyl-3-cephem-4-carboxylic acid of the formula (I.sub.2) ##STR42## wherein --.sup..sym. A represents ##STR43## wherein R.sup.2 is a hydrogen atom or an amino group, and n is an integer of 1 to 2;
- Y.sup..crclbar. represents an anion selected from the group consisting of halogen, sulfonate, benzenesulfonate, acetate, fumarate and citrate anions, which comprises releasing the tri-loweralkylsily protective groups of the tri-loweralkylsilyl derivative represented by the formula ##STR44## wherein --.sup..sym. A represents ##STR45## wherein R.sup.2 is a hydrogen atom or an amino group, and n is an integer of 1 to 2;
- Y.sup..crclbar. represents an anion as indicated above;
- and R.sup.1 represents a lower alkyl group.
Dependencies are inferred from the claim text.