Patent US4182870A successfully refreshed from Google Patents.
US4182870A
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Preparation of 3-bromomethyl-3-cephem sulfoxides
Assignee: Gist Brocades NV
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Filing: 1978-08-30
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Granted: 1980-01-08
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Expires: 1998-08-30
Abstract
Abstract An improved process for the preparation of 3-bromomethyl-3-cephem sulfoxide derivatives of the formula <IMAGE> I wherein R1 is an acylamido group and R2 is a group protecting the carboxy radical which are valuable intermediates for the preparation of various therapeutically useful cephalosporanic acid derivatives.
Inventors
- 👤 Cornelis A. Bruynes
- 👤 Jan J. de Koning
Bibliographic Details
Application Number
—
Jurisdiction
US
Data Source
google_patents
Last Synchronized
2026-10-30 22:27
CPC Classifications
C; C07; C07D; C07D501/00; C07D501/02; C07D501/04; Y; Y02; Y02P; Y02P20/00; Y02P20/50; Y02P20/582
Claims Analysis
Total Claims: 17
Claim 1
Independent Claim
234 words
A process for the preparation of a compound of the formula ##STR7## wherein R 1 is an acylamino and R 2 is a group protecting the carboxy radical comprising brominating a compound of the formula ##STR8## wherein R 1 and R 2 have the above definition to obtain a mixture of compounds of the formulae ##STR9## and treating the mixture or the compound of formula III with a debrominating agent selected from the group consisting of (a) phosphites of the formula ##STR10## wherein R 3 , R 4 and R 5 are individually selected from the group consisting of straight- or branched-chain alkyl optionally substituted with a chlorine atom and having 1 to 18 carbon atoms, phenyl optionally substituted with a methyl or chlorine, allyl and benzyl; (b) phosphites selected from the group consisting of phenyl neopentylglycol phosphite, poly(dipropyleneglycol) phenyl phosphite, tris 25 phosphite and tris(dipropyleneglycol)phosphite; (c) di- and triphosphites selected from the group consisting of diisodecyl pentaerythritol diphosphite, tetraphenyl dipropyleneglycol diphosphite, distearyl pentaerylthritol diphosphite, diphenyl didecyl (2,2,4-trimethyl-1,3-pentanediol) diphosphite, tetrakis(nonylphenyl)polypropyleneglycol diphosphite and heptakis(dipropyleneglycol) triphosphite; (d) di(lower alkyl) phenylphosphonites; (e) lower alkyl diphenylphosphinites; (f) phosphines and (g) trivalent phosphorus compounds selected from the group consisting of hexamethylphosphorous triamide, 2-ethoxy-4-methyl-1,3,2-dioxaphospholane, 4-methyl-2-piperidino-1,3, 2-dioxaphospholane, diethyl N-methyl-N-phenylphosphoramidite and bis-o-phenylene pyrophosphite and an inorganic salt selected from the group consisting of stannous chloride, sodium sulfite and sodium dithionite in the presence of a hydrogen donor to selectively remove the 2-bromine.
Claim 2
Dependent Claim
234 words
A process for the preparation of a compound of the formula ##STR7## wherein R 1 is an acylamino and R 2 is a group protecting the carboxy radical comprising brominating a compound of the formula ##STR8## wherein R 1 and R 2 have the above definition to obtain a mixture of compounds of the formulae ##STR9## and treating the mixture or the compound of formula III with a debrominating agent selected from the group consisting of (a) phosphites of the formula ##STR10## wherein R 3 , R 4 and R 5 are individually selected from the group consisting of straight- or branched-chain alkyl optionally substituted with a chlorine atom and having 1 to 18 carbon atoms, phenyl optionally substituted with a methyl or chlorine, allyl and benzyl; (b) phosphites selected from the group consisting of phenyl neopentylglycol phosphite, poly(dipropyleneglycol) phenyl phosphite, tris 25 phosphite and tris(dipropyleneglycol)phosphite; (c) di- and triphosphites selected from the group consisting of diisodecyl pentaerythritol diphosphite, tetraphenyl dipropyleneglycol diphosphite, distearyl pentaerylthritol diphosphite, diphenyl didecyl (2,2,4-trimethyl-1,3-pentanediol) diphosphite, tetrakis(nonylphenyl)polypropyleneglycol diphosphite and heptakis(dipropyleneglycol) triphosphite; (d) di(lower alkyl) phenylphosphonites; (e) lower alkyl diphenylphosphinites; (f) phosphines and (g) trivalent phosphorus compounds selected from the group consisting of hexamethylphosphorous triamide, 2-ethoxy-4-methyl-1,3,2-dioxaphospholane, 4-methyl-2-piperidino-1,3, 2-dioxaphospholane, diethyl N-methyl-N-phenylphosphoramidite and bis-o-phenylene pyrophosphite and an inorganic salt selected from the group consisting of stannous chloride, sodium sulfite and sodium dithionite in the presence of a hydrogen donor to selectively remove the 2-bromine.
Claim 3
Dependent Claim
15 words
The process of claim 1 wherein the debrominating agent is a trivalent organic phosphorus compound.
Claim 4
Dependent Claim
13 words
The process of claim 1 wherein the debrominating agent is an inorganic salt.
Claim 5
Dependent Claim
27 words
The process of claim 2 wherein the quantity of the debrominating agent is used in excess in relation to the quantity of the compound of formula III.
Claim 6
Dependent Claim
22 words
Process according to claim 3, wherein the debrominating agent is used in equimolar quantity in relation to the compound of formula III.
Claim 7
Dependent Claim
97 words
The process of claim 1 wherein the trivalent organic phosphorus compound is selected from the group consisting of trimethyl phosphite, triethyl phosphite, tripropyl phosphite, triisopropyl phosphite, tributyl phosphite, triisobutyl phosphite, triamyl phosphite, trioctyl phosphite, triisooctyl phosphite, tris (2-ethylhexyl) phosphite, tridecyl phosphite, triisodecyl phosphite, trineodecyl phosphite, trilauryl phosphite, tristearyl phosphite, triallyl phosphite, tris(2-chloroethyl) phosphite, triphenyl phosphite, tris(p-methylphenyl) phosphite, tris-o-tolyl phosphite, tris (p-chlorophenyl) phosphite, 2-ethylhexyl dioctyl phosphite, diethyl benzyl phosphite, didecyl phenyl phosphite, diisodecyl phenyl phosphite, isooctyl diphenyl phosphite, 2-ethylhexyl diphenyl phosphite, decyl diphenyl phosphite, isodecyl diphenyl phosphite, dimethyl phenylphosphonite, diethyl phenylphosphonite, di(t-butyl) phenylphosphonite, methyl diphenylphosphinite and ethyl diphenylphosphinite.
Claim 8
Dependent Claim
100 words
The process of claim 1 wherein the trivalent organic phosphorus compound is selected from the group consisting of trimethyl phosphite, triethyl phosphite, tributyl phosphite, triisooctyl phosphite, triisodecyl phosphite, trilauryl phosphite, tristearyl phosphite, triallyl phosphite, tris(2-chloroethyl) phosphite, triphenyl phosphite, tris-o-tolyl phosphite, tris(p-chlorophenyl) phosphite, 2-ethylhexyl dioctyl phosphite, diethyl benzyl phosphite, isooctyl diphenyl phosphite, 2-ethylhexyl diphenyl phosphite, isodecyl diphenyl phosphite, phenyl neopentylglycol phosphite, poly(dipropyleneglycol)phenyl phosphite, tris 25 phosphite, tris (dipropyleneglycol)phosphite, diisodecyl pentaerythritol diphosphite, tetraphenyl dipropyleneglycol diphosphite, distearyl pentaerythritol diphosphite, diphenyl didecyl (2,2,4-trimethyl-1,3-pentanediol) diphosphite, tetrakis(nonylphenyl) polypropyleneglycol diphosphite, heptakis (dipropyleneglycol) triphosphite, bis-o-phenylene pyrophosphite, hexamethylphosphorous triamide, 2-ethoxy-4-methyl-1,3,2-dioxaphospholane, 4-methyl-2-piperidino-1,3,2-dioxaphospholane, diethyl N-methyl-N-phenylphosphoramidite, diethyl phenylphosphonite, methyl diphenylphosphinite and chlorodiphenylphosphinte.
Claim 9
Dependent Claim
27 words
The process of claim 1 wherein the hydrogen donor is selected from the group consisting of water, a lower alkanol, for example, methanol and a carboxylic acid.
Claim 10
Dependent Claim
12 words
The process of claim 8 wherein the hydrogen donor is acetic acid.
Claim 11
Dependent Claim
20 words
The process of claim 1 wherein R 1 is selected from the group consisting of phenylacetamido, phenoxyacetamido, benzamido and formamido.
Claim 12
Dependent Claim
69 words
The process of claim 1 wherein R 2 is selected from the group consisting of a straight or branched-chain alkyl of 1 to 4 carbon atoms optionally substituted with at least one member of the group consisting of halogen and one to two phenyls, which phenyl groups may themselves carry at least one substituent selected from the group consisting of nitro and methoxy and R 2 is silyl group.
Claim 13
Dependent Claim
11 words
The process of claim 11 wherein R 2 is trilower alkylsilyl.
Claim 14
Dependent Claim
25 words
The process of claim 10 wherein R 2 is selected from the group consisting of methyl, t-butyl, 2-bromoethyl, 2,2,2-trichloroethyl, benzyl, 4-nitrobenzyl, 4-methoxybenzyl, benzhydryl and trimethylsilyl.
Claim 15
Dependent Claim
32 words
The process of claim 1 wherein the compound of formula III is separated from the reaction mixture, optionally purified and treated with a debrominating agent in the presence of a hydrogen donor.
Claim 16
Dependent Claim
18 words
A compound selected from the group consisting of t-butyl 7-benzamido-2-bromo-3-bromomethyl-3-cephem-4-carboxylate 1-oxide, 2,2,2-trichloroethyl 7-formamido-2-bromo-3-bromomethyl-3-cephem-4-carboxylate 1-oxide and methyl 2-bromo-3-bromomethyl-7-phenylacetamido-3-cephem-4-carboxylate 1-oxide.
Claim 17
Dependent Claim
18 words
A compound selected from the group consisting of t-butyl 7-benzamido-2-bromo-3-bromomethyl-3-cephem-4-carboxylate 1-oxide, 2,2,2-trichloroethyl 7-formamido-2-bromo-3-bromomethyl-3-cephem-4-carboxylate 1-oxide and methyl 2-bromo-3-bromomethyl-7-phenylacetamido-3-cephem-4-carboxylate 1-oxide.
References Cited (Backward Citations)
US4042585A
Cited
USPTO Annuity & Maintenance Windows
| Annuity Stage | Window Opens | Payment Deadline | Surcharge Period Until | Estimated Fee | Status |
|---|---|---|---|---|---|
| 3.5 Years (Year 4) | 1983-01-07 | 1983-07-09 | 1984-01-08 | $2000.00 | Window Closed / Lapsed |
| 7.5 Years (Year 8) | 1987-01-07 | 1987-07-09 | 1988-01-08 | $3760.00 | Window Closed / Lapsed |
| 11.5 Years (Year 12) | 1991-01-07 | 1991-07-09 | 1992-01-08 | $7700.00 | Window Closed / Lapsed |