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US4283531A
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Synthesis of β-lactams having a substituted hydroxymethylene group at the position α to the lactam carbonyl group
Assignee: Merck Sharp & Dohme LLC
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Filing: 1979-10-04
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Granted: 1981-08-11
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Expires: 1999-10-04
Abstract
Abstract β-Lactams having a substituted hydroxymethylene group at the position α to the lactam carbonyl group are prepared by reaction of an α-halo-β-lactam with zinc or zinc amalgam in an anhydrous aprotic medium to produce an intermediate which in situ reacts with an appropriate aldehyde or ketone. Also described are novel penicillins and cephalosporins having useful antibacterial activity.
Inventors
- 👤 Ashit K. Ganguly
- 👤 Viyyoor M. Girijavallabhan
- 👤 Patricia Cavender
- 👤 Olga Sarre
- 👤 Stuart W. McCombie
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-23 14:30
CPC Classifications
C; C07; C07D; C07D487/00; C07D487/02; C07D487/04; C07D477/00; C07D477/02; C07D477/10; C07D499/00; C07D503/00; C07D505/00
Claims Analysis
Total Claims: 15
Claim 1
Independent Claim
171 words
The process for preparing and isolating a β-lactam having a substituted hydroxymethylene group at the position α to the lactam carbonyl group of the following formulae: ##STR44## wherein R and R 1 together with the carbon atom to which they are attached is the carbon residue of an aldehyde or ketone which contains no functional group that would preferentially react with a zinc halo-β-lactam intermediate over the oxo functionality; and wherein R 2 is a group of the formula --(CH.sub.2).sub.m --X.sub.p --(CH.sub.2).sub.n -- wherein X is O or S; m is 0-3; n is 0-3; p is 0-1; with the proviso that that m+n+p is 3-5; which comprises the reaction of an α-halo-β-lactam wherein halo is chlorine, bromine or iodine, with zinc or zinc amalgam in an anhydrous aprotic medium at temperatures in the range of from about 0° C. to about 110° C., in the presence of an appropriate aldehyde or ketone, and breaking the zinc complex by the addition of water or a buffer of PH of about 5-7.
Claim 2
Dependent Claim
171 words
The process for preparing and isolating a β-lactam having a substituted hydroxymethylene group at the position α to the lactam carbonyl group of the following formulae: ##STR44## wherein R and R 1 together with the carbon atom to which they are attached is the carbon residue of an aldehyde or ketone which contains no functional group that would preferentially react with a zinc halo-β-lactam intermediate over the oxo functionality; and wherein R 2 is a group of the formula --(CH.sub.2).sub.m --X.sub.p --(CH.sub.2).sub.n -- wherein X is O or S; m is 0-3; n is 0-3; p is 0-1; with the proviso that that m+n+p is 3-5; which comprises the reaction of an α-halo-β-lactam wherein halo is chlorine, bromine or iodine, with zinc or zinc amalgam in an anhydrous aprotic medium at temperatures in the range of from about 0° C. to about 110° C., in the presence of an appropriate aldehyde or ketone, and breaking the zinc complex by the addition of water or a buffer of PH of about 5-7.
Claim 3
Dependent Claim
52 words
The process of claim 1 wherein the halo-β-lactam is of the formula ##STR45## wherein halo is a halogen selected from the group consisting of chlorine, bromine or iodine, R 3 is hydrogen or lower alkoxy, and R 4 is cyano or COOR 11 wherein R 11 is a readily removable esterforming moiety.
Claim 4
Dependent Claim
96 words
The process of claim 1 wherein the halo-β-lactam is of the formula ##STR46## wherein halo is a halogen selected from the group consisting of chlorine, bromine or iodine, R 3 is hydrogen or lower alkoxy, and R 1 is a readily removable ester-forming moiety, R 5 is hydrogen, lower alkanoyloxy, lower alkoxy, lower alkylthio, pyridinium, ##STR47## wherein R 6 , R 7 and R 8 are hydrogen, lower alkyl, phenyl, lower alkylphenyl, halophenyl, hydroxyphenyl, lower alkoxyphenyl, or ##STR48## wherein R 9 and R 10 can be the same or different and are hydrogen or lower alkyl.
Claim 5
Dependent Claim
79 words
The process of claim 1 wherein the halo-β-lactam is of the formula: ##STR49## wherein halo is a halogen atom selected from the group consisting of chlorine, bromine or iodine, R 11 is a readily removable ester-forming moiety, ##STR50## is an attached keto or aldehyde functional group, R 2 is a group of the formula --(CH.sub.2).sub.m --X.sub.p --(CH.sub.2).sub.n wherein X is O or S; m is 0-3; n is 0-3; p is 0-1; with the proviso that m+n+p is 3-5.
Claim 6
Dependent Claim
54 words
The process of claim 1 wherein the halo-β-lactam is of the formula ##STR51## wherein halo is a halogen atom selected from the group consisting of chlorine, bromine or iodine, R 9 and R 10 can be the same or different and/or hydrogen, or lower alkyl, and R 11 is a readily removable ester-forming moiety.
Claim 7
Dependent Claim
35 words
The process of claim 1 wherein the halo-β-lactam is of the formula ##STR52## wherein halo is selected from the group consisting of chlorine, bromine or iodine, and R 11 is a readily removable ester-forming moiety.
Claim 8
Dependent Claim
10 words
The process of claim 1 wherein activated zinc is utilized.
Claim 9
Dependent Claim
10 words
The process of claim 7 wherein the solvent is tetrahydrofuran.
Claim 10
Dependent Claim
10 words
The process of claim 2 wherein the halo-β-lactam is methyl-6α-bromopenicillanate.
Claim 11
Dependent Claim
10 words
The process of claim 2 wherein the halo-β-lactam is benzhydryl-6α-bromopenicillanate.
Claim 12
Dependent Claim
10 words
The process of claim 2 wherein the halo-β-lactam is benzyl-6β-bromo-6α-methoxypenicillanate.
Claim 13
Dependent Claim
10 words
The process of claim 2 wherein the halo-β-lactam is 2,2-dimethyl-3α-cyano-6α-bromopenam.
Claim 14
Dependent Claim
11 words
The process of claim 3 wherein the halo-β-lactam is benzhydryl 7α-bromocephalosporanate.
Claim 15
Dependent Claim
10 words
The process of claim 4 wherein the halo-β-lactam is 6α-oxopropoxy-6β-bromopenicillanate.
References Cited (Backward Citations)
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1984-08-10 | 1985-02-09 | 1985-08-11 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1988-08-10 | 1989-02-09 | 1989-08-11 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1992-08-10 | 1993-02-09 | 1993-08-11 | $7700.00 | Window Closed / Lapsed |