31925-29-8Relevant academic research and scientific papers
METHODS FOR PREPARING FLORFENIOL AND INTERMEDIATE THEREOF
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Paragraph 0111-0113, (2021/07/02)
The present invention discloses a method for preparing florfenicol and its intermediate (V), comprising an addition reaction, a ring closure reaction, a hydrolysis reaction, a ring opening reaction, a reduction reaction, a ring reaction, a fluorination reaction and a ring opening reaction. In the present method for preparing florfenicol, respective reaction steps can be continuously operated, therefore the methods of the present invention features simplified process and shorter synthetic route, and obtained florfenicol has high chiral purity and is of high yield. The method of the present invention for preparing florfenicol (TM) using the intermediate (V) avoids waste water pollution and reduces the cost for treating wastewater and alleviates environmental pollution. At the same time, the methods of the present invention eliminates a chiral resolution procedure, thus increasing the utilization rate of atoms in the reaction. As a result, cost is reduced and process is simplified.
Method for preparing D-p-methylsulfonylphenylserine ethyl ester with high stereoselectivity
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Paragraph 0013; 0015; 0034-0060, (2021/03/13)
The invention discloses a method for preparing D-p-methylsulfonylphenyl serine ethyl ester with high stereoselectivity, which has the advantages of mild reaction conditions, high stereoselectivity andlow corrosivity to production equipment, and belongs to the field of organic reaction catalyzed by small molecules. According to the preparation method provided by the invention, p-methylsulfonylbenzaldehyde and N-Boc glycine ethyl ester are used as basic raw materials, and trifluoromethanesulfonic acid di-n-butyl boron ester is used as an additive, so that optically pure D-type p-methylsulfonylphenylserine ethyl ester is obtained with high stereoselectivity under the condition that Lproline is used as a catalyst. Compared with the existing chemical synthesis method, the method disclosed by the invention has the advantages that the highest total yield of the D-methylsulfonylphenyl serine ethyl ester can reach 75%, and the ee value of the obtained product reaches 73%. The method is low incost and has better yield and optical purity.
Preparation method of (2S, 3R)-p-methylsulfonylphenyl serine ethyl ester
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Paragraph 0016; 0017; 0019; 0027, (2021/02/06)
The invention provides a preparation method of (2S, 3R)-p-methylsulfonylphenyl serine ethyl ester. The preparation method comprises the following steps: dissolving p-methylsulfonyl benzaldehyde and 2-halogenated ethyl acetate serving as raw materials in a solvent A to prepare (2R, 3R)-2-halogen-3-hydroxy-3-(4-methylsulfonyl) phenyl ethyl propionate under the action of a catalyst A, substituting halogen atoms with azide, and performing catalytic hydrogenation reduction to prepare (2S, 3R)-p-methylsulfonyl phenyl serine ethyl ester; or using p-methylsulfonyl benzaldehyde and 2-halogenated ethylacetate as raw materials and dissolving in a solvent B, and preparing (2S, 3S)-2-halogen-3-hydroxy-3-(4-methylsulfonyl) phenyl ethyl propionate under the action of a catalyst B, substituting halogen atoms with benzamide, and preparing (2S, 3R)-p-methylsulfonyl phenyl serine ethyl ester through cyclization, configuration transformation and hydrolysis. The preparation method is high in product purity and high in yield.
Method for preparing florfenicol intermediate and compound obtained by method
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, (2020/07/08)
The invention belongs to the technical field of chemical synthesis and provides a method for preparing a florfenicol intermediate. The method comprises the steps: carrying out a reaction of p-methylthiobenzaldehyde with isocyanoacetate under the catalysis of a chiral catalyst, oxidizing a chiral catalytic product to obtain a methylsulfonyl substituted product, and removing formyl from the methylsulfonyl substituted product to obtain the florfenicol intermediate. According to the preparation method, the chiral center of the intermediate is directly generated through the first-step reaction, theyield of the product in the first step reaches 75-80% and is remarkably higher than the yield obtained through a conventional chiral resolution method (the yield is about 40%), and the chiral purityof the product is high. According to the method, anhydrous cupric sulfate which pollutes the environment is not used, so that the environmental pressure is reduced. In addition, two compounds comprising p-methylthiobenzaldehyde and isocyanoacetate are adopted to react to synthesize the chiral intermediate, so that the material utilization rate and the synthesis efficiency are higher than those ofa linear synthesis means.
Synthesis method of D-p-methylsulfonylphenyl serine ethyl ester
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Paragraph 0008-0009, (2020/01/25)
The invention discloses a synthesis method of D-p-methylsulfonyl phenyl serine ethyl ester. The method comprises the following steps: preparing p-methylsulfonylphenylserine copper by taking p-methylsulfonylbenzaldehyde, copper sulfate and glycine as main raw materials; then adding anhydrous ethanol and concentrated sulfuric acid into an esterification reaction kettle, carrying out heating for a reaction, filtering out copper sulfate while the solution is hot, carrying out cooling for crystallizing, and carrying out filtering to obtain DL p-methylsulfonylphenyl serine ethyl ester sulfate, dissolving the DL p-methylsulfonylphenyl serine ethyl ester sulfate into water, removing copper ions by using a saturated sodium sulfide solution, adding an alkali into the mother solution for dissociationto obtain DL p-methylsulfonylphenyl serine ethyl ester, and adding a resolving agent for resolving to obtain a product. The method is simple in process, high in yield, low in cost and small in environmental pollution and is suitable for enterprise production.
DL-p-methylsulfonylphenyl serine ethyl ester preparation method
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Paragraph 0020-0038, (2020/02/29)
The invention discloses a DL-p-methylsulfonylphenyl serine ethyl ester preparation method, which comprises: 1) adding glycine ethyl ester hydrochloride into ethanol, and carrying out heating reflux; 2) dissolving basic cupric carbonate in ammonia water, and adding into the solution obtained in the step 1); 3) adding KOH into the solution obtained in the step 2) to adjust the pH value of the solution, and adding p-methylsulphonyl benzaldehyde, carrying out a reaction; and 4) after the reaction is finished, recovering ethanol in the reacted substance, adding ammonia water into the residue, regulating the pH value, cooling the solution, filtering, washing with ice water, and drying to obtain the p-methylsulfonylphenyl serine ethyl ester. According to the invention, the target product is generated by carrying out a one-step reaction on glycine ethyl ester hydrochloride and p-methylsulphonyl benzaldehyde under the catalysis of basic cupric carbonate and an alkali, wherein the reaction process does not require the use of concentrated sulfuric acid so as to completely avoid the generation of strong acid wastewater, protect and the environment, avoid the possible danger in the sulfuric acid transportation and production process, achieve the safety and easily improve the operation efficiency.
Characteristics of l-threonine transaldolase for asymmetric synthesis of β-hydroxy-α-amino acids
Xu, Lian,Wang, Li-Chao,Xu, Xin-Qi,Lin, Juan
, p. 5943 - 5952 (2019/11/14)
l-Threonine transaldolase (LTTA) is a putative serine hydroxymethyltransferase (SHMT) that can catalyze the trans-aldehyde reaction of l-threonine and aldehyde to produce l-threo-β-hydroxy-α-amino acids with excellent stereoselectivity. In the present study, an l-threonine transaldolase from Pseudomonas sp. (PsLTTA) was mined and expressed in Escherichia coli BL21 (DE3). A substrate spectrum assay indicated that PsLTTA only consumed l-threonine as the donor substrate and could accept a wide range of aromatic aldehydes as acceptor substrates. Among these substrates, PsLTTA could catalyze p-methylsulfonyl benzaldehyde and l-threonine to produce l-threo-p-methylsulfonylphenylserine with a high conversion rate (74.4%) and a high de value (79.9%). The conversion and stereoselectivity of PsLTTA were found to be dramatically influenced by the concentration of the whole cell, the co-solvent and the reaction temperature. Through conditional optimization, l-threo-p-methylsulfonylphenylserine was obtained with 67.1% conversion and a near-perfect de value (94.5%), the highest stereoselectivity for an l-threo-β-hydroxy-α-amino acid so far reported by enzymatic synthesis. Finally, synthesis of l-threo-p-methylsulfonylphenylserine at a 100 mL scale by whole-cell biocatalysis was conducted. This is the first systematic report of l-threonine transaldolase as a robust biocatalyst for preparation of β-hydroxy-α-amino acids, which can provide new insights for β-hydroxy-α-amino acids synthesis.
Method for preparing chiral (2S,3R)-p-methyl sulfone phenyl ethyl serinate
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Paragraph 0032; 0033, (2019/06/30)
The invention provides a method for preparing (2S, 3R)-p-methyl sulfone phenyl ethyl serinate from the cheap and easily available methylsulfonyl benzaldehyde and L-threonine under the action of transaldolase. The amino acid intermediate then undergoes ethyl esterification to obtain a target product (2S, 3R)-p-methyl sulfone phenyl ethyl serinate.
P-Methyl sulfone phenyl ethyl serinate and synthetic method thereof
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Paragraph 0017; 0040; 0045-0059, (2018/09/12)
The invention discloses a synthetic method of P-methyl sulfone phenyl ethyl serinate, comprising the steps of S1, adding ethyl glycinate hydrochloride into methanol, and heating to dissolve to form afirst solution; S2, adding copper sulfate pentahydrate in the first solution to form a second solution by dissolving; S3, adjusting PH value of the second solution to meet the condition for alkaline reaction, adding P-methylsufonyl benzaldehyde to allow reaction, and holding the temperature and controlling the PH value to keep reaction condition values during reaction; S4, recycling methanol in the reacted materials, adding water to the residue to form a third solution, cooling, and centrifugally separating to obtain P-methyl sulfone phenyl ethyl serinate. The ethyl glycinate hydrochloride andP-methylsufonyl benzaldehyde are subjected to further reaction under the catalytic action of copper sulfate and an organic base to generate a target product; no sulfuric acid is used in the reactionprocess, the amount of waste acid in waste water is decreased, and the environment is protected; dangers that may occur during sulfuric acid transport and production are avoided, better safety is provided, and operating efficiency can be improved.
