76639-93-5Relevant articles and documents
Method for synthesis of florfenicol
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, (2017/08/27)
The invention discloses a method for synthesis of florfenicol and belongs to the technical field of medicine synthesis. 1-R1-2-(R)-4- methylsulfino phenyl formyl aziridine is dissolved in solvent to react with sterically hindered reductant to form chiral alkamine compound 1 with a single configuration; compound 1 is heated and reacts with triethylamine hydrofluoride in the solvent to form (1R, 2S)-3-fluoride-1-4-(methylsulfino phenyl)-2-(R1-amido)-1-propyl alcohol; (1R, 2S)-3-fluoride-1-4-(methylsulfino phenyl)-2-(R1-amido)-1-propyl alcohol has the blocking group taken away in the solvent to form (1R 2S)-2-amido-3-fluoride-1-4-methylsulfino phenyl-1-propyl alcohol; florfenicol can then be obtained through dichloro-acetylation reaction of (1R, 2S)-2-amido-3-fluoride-1-4-methylsulfino phenyl-1-propyl alcohol.
FLORFENICOL SYNTHESIZING METHOD
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Paragraph 0120; 0121, (2016/11/17)
The present invention discloses a new florfenicol synthesizing method. The method synthesizes florfenicol products meeting requirements of the Drug Administration by a series of combinations of cyclization, selective reduction, fluorinated open ring, deprotection and acylation, hydroxyl sulfoacid esterified configuration converting reaction, hydrolysis reaction and the like. The synthesizing method of the present invention utilizing chiral amine closed-ring aziridine three-membered ring uses a physical separation method to repeatedly purify chiral aminoketone of high yield obtaining single R configuration, and uses selective reduction and converts the configuration to obtain florfenicol, greatly improving atom economy, while avoiding waste water pollution caused by the existing process, and greatly reducing costs for treating waste water and reducing pollution to the environment, thus lowering costs and simplifying the process. In addition, the present invention uses triethylamine hydrofluoride as a fluorinated open-ring reagent, to improve safety of a liquid reaction compared to a gas reaction and reduce corrosion of equipment, facilitating industrial production.
Catalytic asymmetric transfer hydrogenation/dynamic kinetic resolution: an efficient synthesis of florfenicol
Wang, Xinlong,Xu, Lingjun,Yan, Lingjie,Wang, Haifeng,Han, Sheng,Wu, Yan,Chen, Fener
, p. 1787 - 1793 (2018/03/29)
A robust and practical method has been developed for the synthesis of florfenicol (1) starting from commercial available 4-(methylsulfonyl) benzoic acid. The key step in this synthesis was the Ru-chloramphenicol base catalyzed asymmetric transfer hydrogenation of N-Boc α-amino-β-ketoester 5 through a dynamic kinetic resolution, which afforded the key chiral building block, anti-(2S,3S)-α-Boc-amino-β-hydroxyl ester 4, with high diastereoselectivity (92% de) and enantioselectivity (78% ee). The synthesis of a series of novel chloramphenicol base ligands L1–L10 is also included. This protocol could also be used for the asymmetric synthesis of fully synthetic analogs of florfenicol.
A substituted 1,2-aminoalcohols method for preparation of drug
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Paragraph 0094; 0095, (2016/10/07)
The invention discloses a preparation method of a substituted 1, 2-alkamine medicine. The preparation method comprises the following steps: dissolving a compound A into a solvent, then adding alkali, stirring, dripping a carbonylation agent, and after dripping, stirring, so as to obtain a compound B; dissolving the compound B into the solvent, adding a reducing agent, controlling the temperature of a reaction liquid to range from 10 DEG C below zero to 50 DEG C, and stirring, so as to obtain a compound C; adding the compound C into the solvent, using Ishikawa agent for fluoridation, after fluoridation, obtaining a compound D, removing the solvent, directly adding into acid for hydrolysis so as to obtain a compound E; resolving the compound E, ester and alkali into the solvent for reaction for 2 to 24 hours under a temperature of 0 to 50 DEG C, so as to obtain a compound F; the process route has the characteristics of short production period, low cost and high yield, the operation is simple and convenient, the product yield is increased while unit operation is shortened, and the preparation method is suitable for industrial production.
Chlorination of florfenicol (FF): reaction kinetics, influencing factors and by-products formation
Zhang, Yansen,Shao, Yisheng,Gao, Naiyun,Chu, Wenhai,Chen, Juxiang,Li, Shuo,Wang, Yue,Xu, Shuaixian
, p. 107256 - 107262 (2016/11/25)
Florfenicol (FF) is a widely used antibiotic, which is commonly found in natural waters. In this study, we investigated the removal fate of FF in two different drinking water treatment plants (DWTPs), which suggest that FF was easily transformed by free available chlorine (FAC) and the potential reactions of FF with FAC was the focus of this study. The oxidation kinetics of FF by FAC (7 × 10?4 mol) are very rapid with large pseudo-first-order rate constants kobs = 0.31 min?1, while FF (5 mg L?1) can be completely transformed in 30 min. The results showed that high Cl? (the dominant seawater constituent), Br?, and lower humic acid (HA, main constituents in freshwater) favor the FF oxidation. 21 degradation products were identified by liquid chromatography-tandems mass spectrometry (LC-MS/MS) and the possible routes for FF chlorination were proposed. These results are of importance toward the goal of assessing the persistence of FF in water chlorination.
MONOMERS CAPABLE OF DIMERIZING IN AN AQUEOUS SOLUTION, AND METHODS OF USING SAME
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Paragraph 0384; 0385, (2014/07/22)
Described herein are monomers capable of forming a biologically useful multimer when in contact with one, two, three or more other monomers in an aqueous media. In one aspect, such monomers may be capable of binding to another monomer in an aqueous media (e.g. in vivo) to form a multimer, (e.g. a dimer). Contemplated monomers may include a ligand moiety, a linker element, and a connector element that joins the ligand moiety and the linker element. In an aqueous media, such contemplated monomers may join together via each linker element and may thus be capable of modulating one or more biomolecules substantially simultaneously, e.g., modulate two or more binding domains on a protein or on different proteins.
A novel no-carrier-added submicromolar scale radiosynthesis of [S-methyl-14C]-florfenicol
Srinivas,Prabhakar,Unny,Sudhakar,Mukkanti,Choudary
, p. 382 - 384 (2013/08/23)
In this paper is reported a novel reaction scheme for the no-carrier-added submicromolar scale radiosynthesis of [S-methyl-14C]-florfenicol that has been newly designed, developed and employed by us successfully. The [ 14C]-product was obtained in an overall radiochemical yield of 30% based on [14C]-methyl iodide taken for the reaction with a radiochemical purity of more than 96%. The specific activity of the product was ~50 mCi (1.85 GBq)/mmol. Chlorosulfonation of compound I was followed by sodium salt formation in situ and it was succeeded by the introduction of [ 14C]-methyl group by coupling with [14C]-CH3I. Subsequently, the oxazolidin-2-one protecting group was opened up by a reaction with sulfuric acid in dioxane and later, the amino group was dichloroacetylated with methyl-2,2-dichloroacetate in triethylamine to obtain [S-methyl- 14C]-florfenicol. A novel method employing a newly designed reaction scheme for the no-carrier-added submicromolar scale radiosynthesis of [S-methyl-14C]-florfenicol has been developed and reported in this paper. An overall radiochemical yield of 30% based on [14C]-methyl iodide was obtained. The radiochemical purity of the final product obtained was more than 96% and specific activity was ~50 mCi (1.85 GBq)/mmol. Copyright
An efficient enantioselective synthesis of florfenicol based on sharpless asymmetric dihydroxylation
Wang, Zhong-Hua,Zheng, Chen,Li, Feng,Zhao, Lei,Chen, Fen-Er,He, Qiu-Qin
, p. 699 - 704 (2012/04/04)
An efficient and highly enantioselective synthesis of florfenicol- via a new intermediate threo-dihydroxy ester, with a Sharpless asymmetric dihydroxylation as the key step, is reported. A ring-opening/reduction strategy avoids the formation of a chlorinated byproduct that occurs in Schumachers phenyloxazoline procedure. The overall yield of florfenicol by this new process is 23% based on 4-(methylsulfonyl)benzaldehyde. Georg Thieme Verlag Stuttgart · New York.
An efficient enantioselective synthesis of florfenicol via asymmetric aziridination
Wang, Zhonghua,Li, Feng,Zhao, Lei,He, Qiuqin,Chen, Fener,Zheng, Chen
, p. 9199 - 9203 (2011/12/01)
An efficient enantioselective synthesis of florfenicol is accomplished in 44.7% overall yield from commercially available p-(methylsulfonyl)benzaldehyde. Key features of this synthesis are the asymmetric aziridination reaction mediated by the Wulff's catalyst in situ derived from (R)-VANOL and diastereoselectively ring-opening of (2S,3S)-fluoroaziridine 13.
PROCESS FOR PREPARING OXAZOLINE-PROTECTED AMINODIOL COMPOUNDS USEFUL AS INTERMEDIATES TO FLORFENICOL
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Page/Page column 49, (2010/04/03)
Processes for preparing oxazoline compounds are disclosed. These oxazoline compounds are useful intermediates in the preparation of Florfenicol and related compounds.
