# US 5,350,845 A · Process for preparing 7-substituted-amino-3-hydroxy-3-cephem-4-protected carboxy-sulfoxide esters

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- Number: US 5,350,845 A
- Document ID: US5350845A
- Status: Granted
- Kind: A
- Application number: 07/976,592
- Filed: 1992-11-13
- Granted: 1994-09-27
- Earliest claimed: 1992-04-08
- Assignees: Eli Lilly and Company
- Inventors: Frank Brown, Jr.
- Web page: https://patentgrep.com/patent/US5350845A

## 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
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

A process for the conversion of a 4-chlorosulfonyl azetidinone (a) to a 3-hydroxy-3-cephem-sulfoxide ester (d) by subjecting an intermediate comprising a tin containing Lewis acid-type Fiedel-Crafts catalyst and 3-exomethylene cepham to ozonolysis.

## Claims

### Claim 1

A process for the preparation of a compound of the formula ##STR36## wherein A is an amino protecting group or a group of the formula ##STR37## wherein R is the residue of a carboxylic acid RCOOH; and R.sub.1 is a carboxy-protecting group, comprising the step of reacting an intermediate complex comprising a tin-containing Lewis acid-type Friedel-Crafts catalyst and a compound of the formula (2) ##STR38## with ozone, under substantially anhydrous conditions.

### Claim 2 (depends on 1)

The process as recited in claim 1 wherein the catalyst is stannic chloride.

### Claim 3 (depends on 1)

The process as recited in claim 1 wherein A is of the formula ##STR39## and R is ##STR40##

### Claim 4 (depends on 1)

The process as recited in claim 1 wherein R.sub.1 is 4-nitrobenzyl.

### Claim 5 (depends on 1)

The process as recited in claim 1 wherein the ozonolysis takes place in the presence of ethyl acetate or methylene chloride.

### Claim 6 (depends on 1)

The process as recited in claim 1 wherein the ozonolysis takes place at a temperature of between about -70.degree. to about -5.degree. C.

### Claim 7 (depends on 6)

The process as recited in claim 6 wherein the solvent is ethyl acetate.

### Claim 8 (depends on 7)

The process as recited in claim 7 wherein the catalyst is stannic chloride, R.sub.1 is p-nitrobenzyl, and A is ##STR41##

### Claim 9 (depends on 1)

The process as recited in claim 1 wherein the ozonolysis takes place at a temperature of between about -50.degree. to about -35.degree. C.

### Claim 10 (depends on 1)

The process as recited in claim 1 further comprising reducing the compound of formula (1) to result in a compound of the formula (3). ##STR42##

### Claim 11 (depends on 10)

The process as recited in claim 10 further comprising chlorinating the compound of formula (3) to give a compound of the formula (4) ##STR43##

### Claim 12 (depends on 11)

The process as recited in claim 11 further comprising deesterifying the compound of formula (4) to obtain a compound of formula (5) ##STR44##

### Claim 13 (depends on 12)

The process as recited in claim 12 where A is of the formula ##STR45##

### Claim 14

In a process for preparing a compound the formula (1) ##STR46## wherein A is an amino protecting group of the formula ##STR47## wherein R is the residue of a carboxylic acid RCOOH and R.sub.1 is a carboxy protecting group, by reacting a compound of the formula ##STR48## wherein R.sub.5 is ##STR49## or imido, with a tin-containing Lewis acid-type Friedel-Crafts catalyst, said reacting forming an intermediate complex comprising the catalyst and a compound of the formula (2) ##STR50## the improvement characterized in ozonizing the intermediate complex without any substantial prior isolation of the compound of formula (2).

### Claim 15 (depends on 14)

The process as recited in claim 14 wherein A is ##STR51## R.sub.1 is p-nitrobenzyl; and the catalyst is stannic chloride.

### Claim 16 (depends on 14)

The process as recited in claim 14 further comprising reducing the compound of formula (1) to result in a compound of formula (3) ##STR52##

### Claim 17 (depends on 16)

The process as recited in claim 16 further comprising chlorinating the compound of formula (3), and thereafter desterifying the resultant compound to obtain a compound of formula (5) ##STR53##

### Claim 18 (depends on 14)

The process as recited in claim 14 wherein said ozonolysis takes place in the presence of ethyl acetate, and at a temperature of -50.degree. to -35.degree. C.