# US 5,708,165 A · Cephem compound, its production and its use for producing cephem antibiotics

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- Number: US 5,708,165 A
- Document ID: US5708165A
- Status: Granted
- Kind: A
- Application number: 08/273,912
- Filed: 1994-07-12
- Granted: 1998-01-13
- Earliest claimed: 1993-07-14
- Assignees: Sumitomo Chemical Company, Limited
- Inventors: Mari Yuasa; Kazuyuki Yamagata; Hirokazu Murata; Masashi Komatsu; Isao Yoshida
- Web page: https://patentgrep.com/patent/US5708165A

## CPC

- C07D 501/00: Heterocyclic compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula: [IMAGE cpc-sch-C07D-0993.gif] , e.g. cephalosporins; Such ring systems being further condensed, e.g. 2,3-condensed with an oxygen-, nitrogen- or sulfur-containing hetero ring
- Y02P 20/55: Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)
- Y02P: CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS

## Abstract

A 3-›(E)-1-propenyl!cephem compound represented by formula (I): ##STR1## wherein R represents hydrogen, a protective group for an amino group, or the group shown by formula (II): ##STR2## in which R.sup.3 is a protective group for an amino group, R.sup.4 is a protective group for a hydroxyl group, and W is --CH.dbd. or --N.dbd.; R.sup.2 represents a protective group for a carboxyl group; and X represents hydrogen or chlorine. The compound is useful as an intermediate for producing cephem antibiotics and is prepared by isomerizing the corresponding 3-›(Z)-1-propenyl!cephem compound in an inert organic solvent in the presence of an aromatic thiol. The compound of formula (I) wherein X is chlorine can be converted into a 3-›(E)-3-ammonio-1-propenyl!cephem derivative through the reaction with a tertiary amine.

## Claims

### Claim 1

A process for producing a 3-›(E)-1-propenyl!cephem compound represented by formula (I): ##STR12## wherein R is hydrogen, a protective group for an amino group or a group shown by formula (II): ##STR13## wherein R.sup.3 is a protective group for an amino group, R.sup.4 is a protective group for a hydroxyl group, and W is --CH.dbd. or --N.dbd.;
R.sup.2 is a protective group for a carboxyl group, and
X is hydrogen or chlorine;
which comprises isomerizing a 3-›(Z)-1-propenyl!cephem compound represented by formula (III): ##STR14## wherein R, R.sup.2 and X are as defined above, in an inert organic solvent in the presence of an aromatic thiol.

### Claim 2 (depends on 1)

A process according to claim 1, which is carried out in the coexistence of a radical initiator selected from the group consisting of an azo compound and a peroxide.

### Claim 3

A process for producing a 3-›(E)-3-ammonio-1-propenyl!cephem compound represented by formula (V): ##STR15## wherein R.sup.11 is a protective group for an amino group or a group represented by formula (II): ##STR16## wherein R.sup.3 is a protective group for an amino group, R.sup.4 is a protective group for a hydroxyl group, and W is --CH.dbd. or --N.dbd.;
R.sup.2 is a protective group for a carboxyl group;
--N.tbd.Q is an organic quaternary ammonio group; and,
Y is a halogen atom;
which comprises reacting a 3-›(E)-3-chloro-1-propenyl!cephem compound represented by formula (Ib): ##STR17## wherein R.sup.11 and R.sup.2 are as defined above, with a tertiary amine in the presence of an iodide or a bromide.

### Claim 4 (depends on 3)

A process according to claim 3, wherein the 3-›(E)-3-chloro-1-propenyl!cephem compound shown by formula (Ib) is prepared by isomerizing a 3-›(Z)-1-propenyl!cephem compound represented by formula (IIIb): ##STR18## wherein R.sup.11 is a protective group for an amino group, or a group represented by formula (II) and,
R.sup.2 is a protective group for a carboxyl group; in an inert organic solvent in the presence of an aromatic thiol.

### Claim 5 (depends on 3)

A process according to claim 3, wherein the tertiary amine is 2-(ethylmethylamino)acetamide.