(1'R,3S,4R)4-acylthio azetidinones
AssigneeFarmitalia Carlo Erba S.p.A.
InventorsWalter Cabri, Ilaria Candiani, Franco Zarini, Angelo Bedeschi
Life of this patent
Estimating the term…
Abstract
There is provided a process for preparing a compound of formula (I) ##STR1## wherein R is H or a hydroxy protecting group, R.sub.2 is an organic residue and R.sub.3 is H or a nitrogen protecting group, which process comprises reacting together a compound of formula (II) ##STR2## wherein R.sub.1 is a C.sub.1 -C.sub.4 alkyl or a phenyl group, R and R.sub.3 are as defined above, a compound of formula (III) ##STR3## wherein R.sub.2 is as defined above and X is a cation or a silicon-containing residue, and a salt of a group IIa, IIb or transition element. The compounds of formula (I) are intermediates in the synthesis of penem antibiotics.
Claims11
A process for preparing a compound of formula (I) having 1'R, 3S, 4R configuration ##STR8## wherein R is H or a hydroxy protecting group, R.sub.2 is:
- (i) a linear, branched or cyclic C.sub.1 -C.sub.6 alkyl group optionally substituted by one or more groups chosen from free and protected hydroxy and amino groups and alkoxy, thioalkyl, C.sub.1 -C.sub.5 alkanoyloxy and carbamoyloxy groups;
- or
- (ii) a 2-pyridyl or 2-tetrahydrofuranyl ring or an aromatic group, optionally substituted by one or more groups chosen from free and protected hydroxy and amino groups and alkoxy, C.sub.1 -C.sub.5 alkanoyloxy, carbamoyloxy and linear or branched C.sub.1 -C.sub.4 alkyl group, the alkyl groups being, in turn, optionally substituted by a free or protected hydroxy or amino group, an alkoxy, C.sub.1 -C.sub.5 alkanoyloxy, carbamoyloxy group, or a pyrrolidinium or pyridinium compound;
- wherein said hydroxy protecting group is a member selected from the group consisting of t-butyl dimethylsilyl, trimethylsilyl, triethylsilyl, pyranyl, acyl, p-nitrovinyloxycarbonyl, and 2,2,2-trichloroethoxycarbonyl;
- and R.sub.3 is H or a nitrogen protecting group, which process comprises reacting together a compound of formula II ##STR9## wherein R.sub.1 is a linear or branched C.sub.1 -C.sub.4 alkyl group or a phenyl group and R and R.sub.3 are as defined above, with 1 to 5 molar equivalents of a compound of formula (III) ##STR10## wherein R.sub.2 is as defined above and X is a cation or a silicon-containing residue of formula --SiR'R"R'" wherein each of R', R" and R'" is, independently, a linear or branched C.sub.1 -C.sub.4 alkyl group, and 0.1 to 5 molar equivalents of a salt of a group IIa, IIb or transition element, wherein said process is carried out in an organic solvent selected from the group consisting of acetonitrile, tetrahydrofuran, dioxane, dimethoxyethane, ethyl acetate and mixtures thereof.
A process for preparing a compound of formula (I) having 1'R, 3S, 4R configuration ##STR11## wherein R is H or a hydroxy protecting group, R.sub.2 is:
- (i) a linear, branched or cyclic C.sub.1 -C.sub.6 alkyl group optionally substituted by one or more groups chosen from free and protected hydroxy and amino groups and alkoxy, thioalkyl, C.sub.1 -C.sub.5 alkanoyloxy and carbamoyloxy groups;
- or
- (ii) a 2-pyridyl or 2-tetrahydrofuranyl ring or an aromatic group, optionally substituted by one or more groups chosen from free and protected hydroxy and amino groups and alkoxy, C.sub.1 -C.sub.5 alkanoyloxy, carbamoyloxy and linear or branched C.sub.1 -C.sub.4 alkyl group, the alkyl groups being, in turn, optionally substituted by a free or protected hydroxy or amino group, an alkoxy, C.sub.1 -C.sub.5 alkanoyloxy, carbamoyloxy group, or a pyrrolidinium or pyridinium compound;
- wherein said hydroxy protecting group is a member selected from the group consisting of t-butyl dimethylsilyl, trimethylsilyl, triethylsilyl, pyranyl, acyl, p-nitrovinyloxycarbonyl, and 2,2,2-trichloroethoxycarbonyl;
- and R.sub.3 is H or a nitrogen protecting group, which process comprises the steps of:
- reacting together a compound of formula II ##STR12## wherein R.sub.1 is a linear or branched C.sub.1 -C.sub.4 alkyl group or a phenyl group and R and R.sub.3 are as defined above, with 1 to 5 molar equivalents of a compound of formula (III) ##STR13## wherein R.sub.2 is as defined above and X is a cation or a silicon-containing residue of formula --SiR'R"R'" wherein each of R', R" and R'" is, independently, a linear or branched C.sub.1 -C.sub.4 alkyl group, and 0.1 to 5 molar equivalents of a salt of a group IIa, IIb or transition element, wherein said reacting step is carried out in an organic solvent selected from the group consisting of acetonitrile, tetrahydrofuran, dioxane, dimethoxyethane, ethyl acetate and mixtures thereof;
- and
- converting the compound of formula (I) into a penem antibiotic.
Dependencies are inferred from the claim text.