# US 9,040,688 B2 · Intermediates in the preparation of 1,4-diphenyl azetidinone

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- Number: US 9,040,688 B2
- Document ID: US9040688B2
- Status: Granted
- Kind: B2
- Application number: 13/260,877
- Filed: 2010-03-31
- Published: 2012-02-02
- Granted: 2015-05-26
- Earliest claimed: 2009-03-31
- Assignees: Lupin Limited
- Applicants: Dhananjai Srivastava; Rajiv Kumar Shakya; Namrata Anil Chaudhari; Inamus Saqlain Ansari; Girij Pal Singh
- Inventors: Dhananjai Srivastava; Rajiv Kumar Shakya; Namrata Anil Chaudhari; Inamus Saqlain Ansari; Girij Pal Singh
- Web page: https://patentgrep.com/patent/US9040688B2

## CPC

- C07D 263/22: with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to other ring carbon atoms
- C07D 205/04: having no double bonds between ring members or between ring members and non-ring members
- C07D 205/08: with one oxygen atom directly attached in position 2, e.g. beta-lactams
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

The process of the present invention relates to a method for the synthesis of a 1,4-diphenylazetidinone of formula (VIII) by using novel oxime intermediates.

## Claims

### Claim 1

A process for the preparation of the compound of formula (VIII),
the process comprising the steps of
a) reacting hydroxylamine or its derivative with a ketone of formula (I) to obtain an oxime of formula (II) wherein R=H, alkyl or silyl;
b) reacting the oxime of formula (II) with an imine of formula (III), wherein R′=H or any phenolic protecting group to obtain β-(substituted-amino)amide of formula (IV);
c) cyclizing the β-(substituted-amino)amide of formula (IV) to form an azetidinone of formula (V);
d) converting the oxime functionality in the compound of formula (V) to a ketone of formula (VI);
e) reducing the ketone functionality of a compound of formula (VI) to the alcohol of formula (VII);
f) removing the phenolic protecting group at any desired stage in the above synthesis.

### Claim 2

A process for the preparation of the compound of formula (VIII),
the process comprising the steps of
a) reacting the oxime of formula (II), wherein R=H, alkyl or silyl; with an imine of formula (III), wherein R′=H or any phenolic protecting group to obtain β-(substituted-amino)amide of formula (IV);
b) cyclizing the β-(substituted-amino)amide of formula (IV) to form an azetidinone of formula (V);
c) converting the oxime functionality in the compound of formula (V) to a ketone of formula (VI);
d) reducing the ketone functionality of a compound of formula (VI) to the alcohol of formula (VII);
e) removing the phenolic protecting group at any desired stage in the above synthesis.

### Claim 3

A process for the preparation of the compound of formula (VIII),
the process comprising the steps of
a) cyclizing the β-(substituted-amino)amide of formula (IV), wherein R=H, alkyl or silyl and R′=H or any phenolic protecting group, to form an azetidinone of formula (V);
b) converting the oxime functionality in the compound of formula (V) to a ketone of formula (VI);
c) reducing the ketone functionality of a compound of formula (VI) to the alcohol of formula (VII);
d) removing the phenolic protecting group at any desired stage in the above synthesis.

### Claim 4

A process for the preparation of the compound of formula (VIII),
the process comprising the steps of
a) converting the oxime of formula (V), wherein R=H, alkyl or silyl and R′=H or any phenolic protecting group, to a ketone of formula (VI);
b) reducing the ketone functionality of a compound of formula (VI) to the alcohol of formula (VII);
removing the phenolic protecting group at any desired stage in the above synthesis.

### Claim 5 (depends on 1)

The process according to claim 1 wherein the hydroxylamine or its derivative that is used in step a) is for protecting the ketone functionality; wherein the cyclization of step c) is carried out in the presence of a silylating agent; wherein converting oxime compound to ketone compound of step d) is carried out in the presence of an acid; and wherein the reduction of step e) is carried out stereo specifically.

### Claim 6 (depends on 2)

The process according to claim 2 wherein the cyclization of step b) is carried out in the presence of a silylating agent; wherein converting oxime compound to ketone compound of step c) is carried out in the presence of an acid; and wherein the reduction of step d) is carried out stereo specifically.

### Claim 7 (depends on 3)

A process according to claim 3 wherein the cyclization of step a) is carried out in the presence of a silylating agent; wherein converting oxime compound to ketone compound of step b) is carried out in the presence of an acid; and wherein the reduction of step c) is carried out stereo specifically.

### Claim 8 (depends on 4)

A process according to claim 4 wherein converting oxime compound to ketone compound of step a) is carried out in the presence of an acid; and wherein the reduction of step b) is carried out stereo specifically.

### Claim 9 (depends on 1)

A process according to claim 1 wherein hydroxylamine is used to protect the ketone functionality.