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Chinese Journal of Organic Chemistry >

2014 , Vol. 34 >Issue 5: 989 - 993

DOI: https://doi.org/10.6023/cjoc201312033

Notes

Synthesis of Major Degradation Products of the Injection of Linezolid

  • Huang Zhixiong ,
  • Sang Zhipei ,
  • Cao Haiyan ,
  • Chao Ruobing ,
  • Deng Yong
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  • a Department of Medicinal Chemistry, West China School of Pharmacy, Sichuan University, Chengdu 610041;
    b Key Laboratory of Drug Targeting and Drug Delivery System, Chengdu 610041

Received date: 2013-12-25

  Revised date: 2014-01-16

  Online published: 2014-02-10

Supported by

Project supported by the Research Fund for the Doctoral Program of Higher Education (No. 20110181110079) and the National Science and Technology Major Project (Nos. 2013ZX09301304-002, 2013ZX09202002).

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Abstract

The ester bond and amide bond of linezolid were selectively hydrolyzed by using LiOH to afford N-[(2R)-3-[[3-fluoro-4-(4-morpholino)phenyl]amino]-2-hydroxypropyl] acetamide (2) and (2S)-1-amino-3-[[3-fluoro-4-(4-morpholino)- phenyl]-amino]-2-propanol (4) with 78.3% and 86.6% yields respectively, which were the partially hydrolyzed impurity and fully hydrolyzed impurity of the injection of linezolid. The terminal amino group of compound 4 was then protected with tert-butyloxycarbonyl and subjected to N,O-diacetylation. Subsequently, N-[(2S)-3-amino-2-hydroxypropyl]-N-[3-fluoro-4-(4-morpholino)phenyl]acetamide (3) hydrochloride was synthesized by removal of O-acetyl with ammonia/methanol and then deprotection tert-butoxycarbonyl using saturated solution of hydrogen chloride in ether with 62.3% overall yield.

Key words： oxazolidinone antibacterial; linezolid; injection; degradation product; impurity; synthesis

Cite this article

Huang Zhixiong , Sang Zhipei , Cao Haiyan , Chao Ruobing , Deng Yong . Synthesis of Major Degradation Products of the Injection of Linezolid[J]. Chinese Journal of Organic Chemistry, 2014 , 34(5) : 989 -993 . DOI: 10.6023/cjoc201312033

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