Patent ID: 6160132
Filing Date: 2000-12-12
Classification: C07C,C07D

Abstract:
A process for the preparation of an intermediate of the formula ##STR9## where R.sup.1 is C.sub.1 -C.sub.12 alkyl, straight or branched and optionally substituted by halogen, hydroxy, C.sub.1 -C.sub.6 alkoxy, amino, carboxyl, C.sub.1 -C.sub.6 alkoxycarbonyl, carboxamido, nitrile, mono- or di-(C.sub.1 -C.sub.6)alkylamino, thio, C.sub.1 -C.sub.6 alkylthio, aryl, --Oaryl or --OCH.sub.2 aryl where aryl is optionally substituted with C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, carboxy, halogen, cyano, nitro, carboxamido, or hydroxy; and C.sub.1 -C.sub.6 alkanesulfonyloxy; Z is H, phenyl or --CR.sup.3 R.sup.4 R.sup.5 where R.sup.3, R.sup.4, and R.sup.5 are independently selected from H, methyl, --O--C.sub.1 -C.sub.12 alkyl, O-tetrahydropyranyl, --S-benzyl and phenyl optionally substituted with methoxy, hydroxy, nitro, or methyl, which comprises:(1) reacting a compound of the formula ##STR10## with iodine to obtain predominantly the (3R, 5R) dihydrofuranone of the formula ##STR11## (2) reacting 3(R)-3-R.sup.1 -5(R)-iodomethyldihydrofuran-2-one of step (1) with a sulfur reagent, HSW, and a base where W is defined as phenyl, --C(O)aryl and --C(O)substituted aryl, where aryl is as defined above; --O--C.sub.1 -C.sub.12 alkyl, or --CR.sup.3 R.sup.4 R.sup.5 where R.sup.3, R.sup.4 and R.sup.5 are independently H, methyl, --O--C.sub.1 -C.sub.12 alkyl, --O--tetrahydropyranyl, --S-benzyl, or phenyl optionally substituted with methoxy, hydroxy, nitro, or methyl to obtain an intermediate of the formula iiib, ##STR12## (3) deprotection of the sulfur of lactone iiib of step (2) under reducing conditions, acid hydrolysis or base hydrolysis, to provide compound ivb (Z.dbd.H), and(4) protection of the free thiol of step (3) above to provide compound ivb where Z is defined as H, phenyl, --CR.sup.3 R.sup.4 R.sup.5 where R.sup.3, R.sup.4 and R.sup.5 are independently H, methyl, --O--C.sub.1 -C.sub.12 alkyl, --O-tetrahydropyranyl, --S-benzyl, or phenyl optionally substituted with methoxy, hydroxy, nitro, or methyl; disulfides or any other group suitable for protecting sulfur.