Claims
- 1. A process for preparing symmetrical azetidinone aldehyde disulfide compounds of the formula ##STR41## which comprises: (1) reacting a 2.alpha.-alkoxy cephalosporin ester of the formula ##STR42## with about 1 to about 1.3 equivalents of an N-chloro halogenating agent in a chlorinated hydrocarbon solvent at a temperature between -10.degree. C. and 30.degree. C.;
- (2) combining the above solution with an aqueous suspension of between about 2 and about 4 molar equivalents of mercury dichloride and about 5 to about 7 molar equivalents of cadmium carbonate at a temperature between about 0.degree. C. and about 30.degree. C.; where in the above formulae R.sub.1 is an acyl group of the formula ##STR43## wherein R' is (a) C.sub.1 -C.sub.7 alkyl, cyanomethyl, C.sub.1 -C.sub.6 haloalkyl, 4-protected amino-4-protected carboxybutyl; or
- (b) C.sub.1 -C.sub.6 alkoxy, phenoxy, benzyloxy or p-methoxybenzyloxy; or
- (c) the group --R" wherein R" is phenyl or substituted phenyl wherein the substituents are 1 or 2 halogens, protected hydroxy, cyano, trifluoromethyl, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, protected carboxy, protected carboxymethyl, protected hydroxymethyl or protected aminomethyl; or
- (d) an arylalkyl group of the formula
- R"--(O).sub.m --CH.sub.2 --
- wherein m is 0 or 2; or
- (e) a substituted arylalkyl group of the formula ##STR44## wherein R'" is R" as defined above, 2-thienyl, 3-thienyl, 2-furyl or 3-furyl; W is protected hydroxy, protected carboxy, protected amino, or
- (f) a heteroarylmethyl group of the formula
- R""--CH.sub.2 --
- wherein R"" is 2-thienyl, 3-thienyl, 2-furyl, 3-furyl, 2-thiazolyl, 5-tetrazolyl, 1-tetrazolyl;
- R.sub.2 is a carboxy protecting group; and R.sub.3 is methyl, ethyl or isopropyl.
- 2. The process of claim 1 wherein R.sub.2 is benzyl, diphenylmethyl, tert-butyl, p-methoxybenzyl, 2,4,6-trimethylbenzyl, trityl, 4-methoxytrityl, 4,4'-dimethoxytrityl, or 4,4',4"-trimethoxytrityl.
- 3. The process of claim 1 wherein R.sub.1 is an acyl group of the formula ##STR45## wherein R' is (a) C.sub.1 -C.sub.7 alkyl, cyanomethyl;
- (b) C.sub.1 -C.sub.6 alkoxy;
- (c) benzyl, 1-phenoxymethyl, 1-p-methoxyphenylmethyl;
- (d) 2-thienylmethyl, 3-thienylmethyl, 2-furylmethyl, 3-furylmethyl, 2-thiazolylmethyl 5-tetrazolylmethyl;
- (e) 1-protected hydroxy-1-phenylmethyl, 1-protected amino-1-phenylmethyl, 1-protected amino-1-(4-protected hydroxyphenyl)methyl.
- 4. The process of claim 3 wherein R.sub.2 is benzyl, diphenylmethyl, tert-butyl, p-methoxybenzyl, 2,4,6-trimethylbenzyl, trityl, 4-methoxytrityl, 4,4'-dimethoxytrityl, or 4,4',4"-trimethoxytrityl.
- 5. The process of claim 4 wherein R.sub.2 is benzyl.
- 6. The process of claim 1 wherein R.sub.1 is an arylalkyl group of the formula ##STR46## wherein R" is phenyl or substituted phenyl wherein the substituents are 1-2 halogens, protected hydroxy, cyano, trifluoromethyl, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, protected carboxy, protected carboxymethyl, protected hydroxymethyl or protected aminomethyl; and m is 0 or 1.
- 7. The process of claim 6 wherein R.sub.2 is benzyl, diphenylmethyl, tert-butyl, p-methoxybenzyl, 2,4,6-trimethylbenzl, trityl, 4-methoxytrityl, 4,4'-dimethoxytrityl, 4,4',4"-trimethoxytrityl.
- 8. The process of claim 7 wherein R.sub.1 is benzyl.
- 9. The process of claim 8 wherein R.sub.2 is benzyl.
- 10. The process of claim 1 wherein R.sub.3 is methyl.
- 11. The process of claims 1, 3 or 6 in which the N-chloro halogenating agent is a compound of the formula ##STR47## in which R.sub.4 is hydrogen, chloro, C.sub.1 -C.sub.3 alkyl, cyclohexyl, phenyl, or phenyl substituted with chloro,
- bromo, methyl, or nitro, and R.sub.5 is R.sub.6 --X-- in which R.sub.6 is C.sub.1 -C.sub.3 alkyl, cyclohexyl, phenyl, or phenyl substituted with chloro, bromo, methyl, or nitro, and X is ##STR48## or --SO.sub.2 --; or R.sub.4 and R.sub.5 taken together with the nitrogen to which they are bonded define a heterocyclic structure of the formula ##STR49## in which Y is o-phenylene, or --(CH.sub.2).sub.n -- in which n is 2 or 3; or a structure of the formula ##STR50## in which Z is Y as hereinbefore defined or a group of the formula ##STR51## in which A is hydrogen or methyl.
- 12. The process of claim 11, in which the N-chloro halogenating agent has the formula ##STR52## in which Y is o-phenylene or --CH.sub.2 --CH.sub.2 --.
- 13. The process of claim 12, in which the N-chloro halogenating agent is N-chlorosuccinimide.
- 14. The process of claim 9 wherein the N-chloro halogenating agent has the formula ##STR53## in which Y is o-phenylene or --CH.sub.2 --CH.sub.2 --.
- 15. The process of claim 14 in which the N-chloro halogenating agent is N-chlorosuccinimide.
Parent Case Info
This application is a division, of application Ser. No. 138,023, filed Apr. 7, 1980 now U.S. Pat. No. 4,293,495.
US Referenced Citations (1)
Number |
Name |
Date |
Kind |
4302391 |
Kukolja |
Nov 1981 |
|
Non-Patent Literature Citations (3)
Entry |
Pfeil et al., J. Organic Chem. 46, 827 (1981). |
Gorden et al., Chem. Abs. 88, 121082d (1977). |
Paquette et al., Syn. Comm. 6, 575 (1976). |
Divisions (1)
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Number |
Date |
Country |
Parent |
138023 |
Apr 1980 |
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