Method for preparing linezolid intermediate

Patent metadata

Field	Value
Publication number	US-9434702-B2
Application number	US-201314378825-A
Country	US
Kind code	B2
Filing date	Feb 8, 2013
Priority date	Feb 15, 2012
Publication date	Sep 6, 2016
Grant date	Sep 6, 2016

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.

First claim

The invention claimed is:

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:

2. 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.

3. 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.

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

5. 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.

6. 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, C 6 -C 8 alkanes, acetone, 1,4-dioxane, acetonitrile, or any mixture thereof.

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

8. 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.

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.

Assignees

• Zhejiang Hisun Pharm Co Ltd
• Shanghai Inst Pharmaceutical Ind
• Zhejiang Hisun Pharamceutical Co Ltd

Inventors

• Zhang Fuli
• Yang Chunbo
• Liang Bin
• Qiu Pengcheng
• Luo Hairong
• Li Jiang
• Chai Jian
• Cai Qingfeng

Classifications

• C07D413/06

  linked by a carbon chain containing only aliphatic carbon atoms · CPC title

• C07D263/20 Primary

  attached in position 2 · CPC title