Process for preparing benzothiazepine derivatives

A process for stereoselectively preparing a cis-form of 1,5-benzothiazepine derivative represented by formula (VI):

• ##STR30## wherein Y represents a member selected from the group consisting of hydrogen, halogen, C.sub.1 -C.sub.6 alkyl, C.sub.3 -C.sub.6 cycloalkyl, C.sub.1 -C.sub.6 alkoxy, aryl, aryl C.sub.1 -C.sub.6 alkyl, aryl C.sub.1 -C.sub.6 alkoxy and aryloxy, the aryl portion of such groups being phenyl or naphthyl,
• n is an integer of 1-6, and
• R.sup.1 represents an amino group represented by the formula:
• --NR.sup.1a R.sup.1b
• wherein
• (1) R.sup.1a and R.sup.1b each independently represents hydrogen or straight or branched C.sub.1 -C.sub.6 alkyl, or
• (2) R.sup.1a and R.sup.1b may form, taken together with the nitrogen to which R.sup.1a and R.sup.1b are attached, a cyclic amino group selected from the group consisting of 1-piperazinyl, 1-piperidyl, 1-pyrrolidinyl, 4-morpholinyl and 4-thiomorpholinyl, said cyclic amino groups being unsubstituted or substituted by unsubstituted or substituted phenyl, C.sub.1 -C.sub.6 alkyl, unsubstituted or substituted phenylalkyl or unsubstituted or substituted diphenylalkyl, the substituents on the substituted phenyl, substituted phenylalkyl and substituted diphenylalkyl being halogen, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy or methylenedioxy and the alkyl portion of said groups being C.sub.1 -C.sub.6 alkyl, the process comprising,
• (1) stereoselectively preparing a threo-form of a compound represented by formula (III):
• ##STR31## by reacting an o-(aminoalkylamino) thiophenol compound represented by formula (I):
• ##STR32## wherein Y, n and R.sup.1 are as defined above, with a trans-3-(4-methoxyphenyl)glicidic ester represented by formula (II):
• ##STR33## wherein R.sup.2 represents lower alkyl, at an elevated temperature in a nonpolar solvent in the presence of a divalent or trivalent iron ion;
• (2) hydrolysing the ester group of the compound obtained in Step (1) to yield a carboxylic acid represented by formula (IV):
• ##STR34## (3) acetylating the 2-hydroxyl group of the carboxylic acid obtained in Step (2) to convert it into a 2-acetoxy compound represented by formula (V):
• ##STR35## (4) subjecting the 2-acetoxy compound obtained in step (3) to a ring closure reaction to convert it into a 1,5-benzothiazepine derivative represented by formula (VI).