# US 9,434,702 B2 · Method for preparing linezolid intermediate

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- Number: US 9,434,702 B2
- Document ID: US9434702B2
- Status: Granted
- Kind: B2
- Application number: 14/378,825
- Filed: 2013-02-08
- Published: 2015-01-08
- Granted: 2016-09-06
- Earliest claimed: 2012-02-15
- Assignees: Zhejiang Hisun Pharamceutical Co., Ltd.; Shanghai Institute of Pharmaceutical Industry
- Applicants: Zhejiang Hisun Pharmaceutical Co., Ltd.; Shanghai Institute of Pharmaceutical Industry
- Inventors: Fuli Zhang; Chunbo Yang; Bin Liang; Pengcheng Qiu; Hairong Luo; Jiang Li; Jian Chai; Qingfeng Cai
- Web page: https://patentgrep.com/patent/US9434702B2

## CPC

- C07D 263/20: attached in position 2
- C07D 413/06: linked by a carbon chain containing only aliphatic carbon atoms
- C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08)

## Abstract

Disclosed is a new method for preparing a methyl substitute of a linezolid intermediate, (S)-2-(3-(3-fluoro-4-morpholinophenyl)-2-oxo-5-oxazoline) (I), wherein the intermediate (I) is obtained by the cyclization of 3-fluoro-4-morpholinophenyl isocyanate (II) and epoxy compound (III). This process has a short process route, low cost, easy operation, and high yield, so is suitable for a large-scale industrial production.

## Claims

### Claim 1

A process for preparing an intermediate of Linezolid of Formula (I):
the process comprises the following steps:
a cyclization reaction of 3-fluoro-4-morpholinophenyl isocyanate (II) and epoxy compound (III) is performed to obtain the compound of Formula (I),
wherein R is a protected amino group as follows:

### Claim 2 (depends on 1)

The process according to claim 1, wherein the cyclization reaction is performed in the presence of a catalyst, preferably, the catalyst is a Lewis acid or a mixture thereof.

### Claim 3 (depends on 2)

The process according to claim 2, wherein the catalyst is selected from lithium bromide, magnesium bromide, lithium chloride, magnesium chloride, magnesium iodide, lithium iodide, lithium chloride, zinc chloride, tetra-n-butylammonium bromide, tetra-n-butylammonium chloride, or any mixture thereof.

### Claim 4 (depends on 2)

The process according to claim 2, wherein the catalyst is selected from lithium bromide, magnesium bromide, magnesium iodide, or any mixture thereof.

### Claim 5 (depends on 1)

The process according to claim 1, wherein the cyclization reaction is performed in a solvent, preferably, the solvent is an aprotic solvent or a mixture thereof.

### Claim 6 (depends on 5)

The process according to claim 5, wherein the aprotic solvent includes but not limited to petroleum ether, ethyl acetate, isoamyl acetate, butyl acetate, toluene, xylene, chlorobenzene, tetrahydrofuran, dichloromethane, N, N-dimethylformamide, C6-C8 alkanes, acetone, 1,4-dioxane, acetonitrile, or any mixture thereof.

### Claim 7 (depends on 1)

The process according to claim 1, wherein the temperature of the cyclization reaction is in the range of 60° C.-150° C.

### Claim 8 (depends on 7)

The process according to claim 7, wherein the temperature of the cyclization reaction is in the range of 100-140° C., particularly preferably 115-125° C.

### Claim 9

A process for preparing linezolid, wherein linezolid is prepared from the intermediate of Formula (I)
wherein the intermediate of Formula (I) is prepared by the reaction as follows:
a cyclization reaction of 3-fluoro-4-morpholinophenyl isocyanate (II) and epoxy compound (III) is performed to obtain the compound of Formula (I), wherein R is a protected amino group as follows:
followed by deprotection and acetylation to obtain linezolid.