Claims
- 1. A process for preparing a compound of the formula ##STR5## wherein X is hydrogen;
- m is 0 or 1;
- R.sup.2 is hydrogen or methoxy;
- R is hydrogen or --COR.sup.3 ;
- R.sup.3 is hydrogen, C.sub.1 --C.sub.3 alkyl, halomethyl, benzyloxy, 2,2,2-trichloroethoxy, t-butoxy, R.sup.4, R.sup.4 --(O).sub.n --CH.sub.2 --, R.sup.4 --CH(R.sup.5)--, R.sup.6 --CH.sub.2 --, or ##STR6## wherein R.sup.7 is hydrogen or C.sub.1 -C.sub.3 alkyl and R.sup.8 is hydrogen or an amino-protecting group;
- R.sup.4 is cyclohexadienyl or phenyl, or cyclohexadienyl or phenyl substituted with one or two halo, hydroxy, protected hydroxy, aminomethyl, protected aminomethyl, C.sub.1 -C.sub.4 alkyl or C.sub.1 -C.sub.4 alkoxy groups;
- n is 0 or 1;
- R.sup.5 is hydroxy, protected hydroxy, amino, protected amino, carboxy or protected carboxy;
- R.sup.6 is 2-thienyl, 2-furyl, 5-tetrazolyl or 1-tetrazolyl;
- R.sup.1 is C.sub.1 -C.sub.4 alkanoyloxy, benzoyloxy, fluoro, chloro, carbamoyloxy, C.sub.1 -C.sub.4 alkylcarbamoyloxy, pyridinio, pyridinio substituted with C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkanoyl, carbamoyl, C.sub.1 -C.sub.4 alkylcarbamoyl, chloro, fluoro, hydroxy or trifluoromethyl, or the corresponding pyridinio chlorides or bromides, or --S--R.sup.9 ;
- R.sup.9 is --CH.sub.2 CO.sub.2 (C.sub.1 -C.sub.4 alkyl), carbamoyl, phenyl, phenyl substituted with one or two chloro, fluoro, C.sub.1 -C.sub.4 alkyl, hydroxy, C.sub.1 -C.sub.4 alkylsulfonamido or trifluoromethyl groups; triazol-3-yl unsubstituted or substituted with one or two groups independently selected from C.sub.1 -C.sub.3 alkyl, --CO.sub.2 (C.sub.1 -C.sub.4 alkyl), --CONH.sub.2 and --CH.sub.2 NHOCO(benzyl or C.sub.1 -C.sub.4 alkyl); ##STR7## tetrazol-1-yl or tetrazol-5-yl substituted with one or two groups independently selected from C.sub.1 -C.sub.4 alkyl and --CH.sub.2 CO.sub.2 (C.sub.1 -C.sub.4 alkyl or hydrogen); 4-cyano-5-aminopyrimidin-2-yl, or 5-methyl-1,3,4-thiadiazol-2-yl;
- provided that n is 0 when R.sup.4 is cyclohexadienyl;
- which process comprises electrolytically reducing a compound of the above formula wherein X is p-nitrobenzyl in an acidic liquid medium comprising from about 0 to about 50% water, an acid having a pK.sub.a determined in water of 0 or below, the amount of said acid being at least four moles per mole of the compound to be reduced, and an organic solvent substantially inert to electrolytic reduction, at the working electrode of an electrolytic cell, said working electrode substantially comprising carbon, mercury, tin, aluminum, silver, copper, lead, chromium, zinc, nickel or cadmium, at a temperature from about 0.degree. C. to about 75.degree. C., at a potential in a range from about the potential of the initial onset of current flow of the first reduction to about the potential of the initial onset of current flow of the second reduction.
- 2. A process of claim 1 wherein the acidic liquid medium comprises from about 10% to about 50% water.
- 3. A process of claim 1 wherein the organic solvent is water-miscible.
- 4. A process of claim 1 wherein the organic solvent is dimethylformamide.
- 5. A process of claim 1 wherein the organic solvent is tetrahydrofuran.
- 6. A process of claim 1 wherein the acid is hydrochloric acid.
- 7. A process of claim 1 wherein the acid is sulfuric acid.
- 8. A process of claim 1 wherein the cell is a divided cell.
- 9. A process of claim 1 wherein the working electrode comprises silver, lead or mercury.
- 10. A process of claim 1 wherein the potential is controlled by means of a reference electrode.
- 11. A process of claim 3 wherein the acidic liquid medium comprises from about 10% to about 50% water.
- 12. A process of claim 11 wherein the organic solvent is dimethylformamide or tetrahydrofuran.
- 13. A process of claim 12 wherein the acid is hydrochloric acid or sulfuric acid.
- 14. A process of claim 13 wherein the working electrode comprises silver, lead or mercury.
- 15. A process of claim 14 wherein the cell is a divided cell.
- 16. A process of claim 15 wherein the potential is controlled by means of a reference electrode.
- 17. A process of claim 3, 4 or 5 wherein the acid is hydrochloric acid or sulfuric acid.
- 18. A process of claim 17 wherein the acidic liquid medium comprises from about 10% to about 50% water.
- 19. A process of claim 2, 3, 4 or 5 wherein the cell is a divided cell.
- 20. A process of claim 19 wherein the working electrode comprises silver, lead or mercury.
- 21. A process of any one of claims 1-16 wherein the product is a compound wherein R.sup.1 is --S--R.sup.9.
- 22. A process of claim 21 wherein R.sup.9 is a triazol-3-yl, tetrazol-1-yl, tetrazol-5-yl or thiadiazol-2-yl group.
- 23. A process of claim 22 wherein the product is a compound wherein R is --COR.sup.3, and R.sup.3 is a R.sup.4, R.sup.4 --(O).sub.n --CH.sub.2 --, or R.sup.4 --CH(R.sup.5)-- group.
- 24. A process of any one of claims 1-16 wherein the product is 7-(tetrazol-1-ylacetamido)-3-(5-methyl-1,3,4-thiadiazol-2-ylthiomethyl)-3-cephem-4-carboxylic acid.
- 25. A process of any one of claims 1-16 wherein the product is 7-(2-phenyl-2-hydroxyacetamido)-3-(1-methyltetrazol-5-ylthiomethyl)-3-cephem-4-carboxylic acid.
CROSS-REFERENCE
This application is a continuation-in-part of my co-pending application Ser. No. 135,829, filed Mar. 31, 1980, now abandoned.
US Referenced Citations (3)
Non-Patent Literature Citations (3)
Entry |
Mairanovsky, Angev. Chem. Int. Ed. Engl., vol. 15, No. 5, pp. 281-292 (1976). |
Otaka et al., Chem. Abs., vol. 85, Abs. 160124b (1976). |
Cephalosporins and Penicillins by Flynn, pub. by Acedemic Press (1972), pp. 147-151. |
Continuation in Parts (1)
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Number |
Date |
Country |
Parent |
135829 |
Mar 1980 |
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