Tanabe Seiyaku Company, Limited

Shigeru Nishimoto

Akio Nakao

Yasuji Ikeda

Hiroyuki Nate

Ikuo Iijima

Mitsunori Gaino

Masaru Senuma

Hironori Hayashi

Sadao Maeda

Nobuhiko Ishihara

Tamotsu Okuno

Eisaku Yamato

Noboru Shigematsu

Tokuo Fujii

Masashi Kitano

Kuichiro Ikeda

This disclosure describes a process for the preparation of 1,5-benzothiazepinone derivatives. The process involves the use of sulfonic acids as catalysts to effect ring closure to form the 1,5-benzothiazepinone ring. The resulting compounds have well known pharmaceutical properties.

Process for preparing 1,5-benzothiazepine derivatives

There is disclosed a process for preparing 1,5-benzothiazepine derivatives represented by the formula: ##STR1## wherein one of R.sup.1 and R.sup.2 is a lower alkyl group or halogen atom, and the other is hydrogen atom, R.sup.3 is a lower alkyl group or a lower alkoxy group, which comprises subjecting a propionic acid compound represented by the formula (II): ##STR2## wherein R.sup.1, R.sup.2 and R.sup.3 have the same meanings as defined above, and R.sup.4 represents hydrogen atom or an ester residue, to intramolecular ring closing reaction in the presence of a sulfonic acid compound represented by the formula (III):

A benzothiazepine derivative of the formula: ##STR1## wherein R is hydrogen or acetyl, is prepared by condensing a compound of the formula: ##STR2## wherein R is the same as defined above, with 2-(diamethylamino)ethyl halide (i) in the presence of potassium hydroxide in acetone; or (ii) in the presence of potassium carbonate in acetone, lower alkyl acetate, a mixture of acetone and water or a mixture of lower alkyl acetate and water.

Method of preparing benzothiazepine derivatives

Glyoxylic acid or a salt of glyoxylic, an ammonium salt of an organic or inorganic acid and a phenol compound of the formula: ##STR1## wherein n is an integer of one to three, are condensed together to prepare hydroxyphenylglycine compounds of the formula: ##STR2## wherein n is the same as defined above. The hydroxyphenylglycine compounds thus obtained are useful as intermediates in the synthesis of penicillins and cephalosporins.

Process for preparing a hydroxyphenylglycine compound

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Minoo, Japan

Shigeru Nishimoto