CN111116364A - Process for preparing 2-polyhaloacetyl-3-alkoxy acrylate - Google Patents
Process for preparing 2-polyhaloacetyl-3-alkoxy acrylate Download PDFInfo
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Abstract
The invention discloses a preparation method of 2-polyhalogenated acetyl-3-alkoxy acrylic ester, which comprises the steps of dissolving a compound with a chemical structural formula II in an organic solvent, cooling to-30-0 ℃, dropwise adding the compound with the chemical structural formula I under the action of an acid-binding agent, carrying out a first-stage reaction for 0.5-4h, then heating to 0-50 ℃, carrying out a second-stage reaction, and reacting for a certain time to generate the 2-polyhalogenated acetyl-3-alkoxy acrylic ester with the chemical structural formula III. The method has the advantages of low cost, reasonable process, simple and convenient operation and high atom economy, and can meet the requirements of industrial application.
Description
Technical Field
The invention relates to a preparation method of 2-polyhalogenated acetyl-3-alkoxy acrylate.
Background
Since the 21 st century, the application of fluorine-containing pyrazolecarboxamide compounds in medicines and pesticides has attracted very wide attention, and researches have found that the pyrazolecarboxamide compounds with difluoro methyl substituents can significantly improve the biological activity of organic compounds, so that a plurality of pesticide research and development personnel are attracted to develop wide and deep research and research on the innovative field, and medicaments such as pyrazolecarboxamide, cyprodinil, fluopicolide, bixafen and the like are successively introduced by pionorda, basf and Bayer abroad, have the characteristics of unique mechanism and high efficiency, and have very wide prospects.
In the chemical synthesis of the compounds, 2-polyhaloacetyl-3-alkoxy acrylate (polyhalo is one of difluoro, trifluoro, dichloro and trichloro; alkoxy is one of methoxy and ethoxy) is an important intermediate for synthesizing low-toxicity and high-efficiency bactericides containing fluorine pyrazolecarboxamide such as pyrazolonaphthoramide and the like. With the wide use of difluoropyrazolecarboxamide bactericides, the demand on 2-polyhaloacetyl-3-alkoxy acrylate is remarkably increased, and the content and yield of the difluoropyrazolecarboxamide bactericides directly influence the production cost and the product quality of the fluorine-containing pyrazolecarboxamide bactericides such as isopyrazam and the like.
Through the summary of the synthetic route of the 2-polyhaloacetyl-3-alkoxy acrylate, we can find that the method for synthesizing the 2-polyhaloacetyl-3-alkoxy acrylate reported in the literature has the defects of high raw material cost, low atom utilization rate and the like. Taking 2-difluoroacetyl-3-ethoxy ethyl acrylate as an example, the current synthetic process route is as follows:
the synthetic route uses triethyl orthoformate in synthesis, so that the price is high, the atom utilization rate is low, and sodium methoxide and acetic anhydride are difficult to recycle after the sodium methoxide and acetic anhydride are used, so that the post-treatment cost is greatly increased.
Therefore, it is necessary to develop a synthetic route with more industrial value, reduce the production cost, and increase the yield of the target product to meet the industrial demand.
Disclosure of Invention
In order to solve the problems in the prior art, the invention provides a preparation method of 2-polyhalogenated acetyl-3-alkoxy acrylate, develops a synthetic route with industrial value, and has the advantages of low cost, reasonable process, simple and convenient operation, high atom economy and less three-waste discharge.
In order to achieve the purpose, the technical scheme adopted by the invention is a preparation method of 2-polyhalogenated acetyl-3-alkoxy acrylate, a compound with a chemical structural formula II is dissolved in an organic solvent, the temperature is reduced to-30-0 ℃, the compound with the chemical structural formula I is dropwise added under the action of an acid-binding agent, the first-stage reaction is carried out for 0.5-4h, then the temperature is raised to 0-50 ℃, the second-stage reaction is carried out, and the 2-polyhalogenated acetyl-3-alkoxy acrylate with the chemical structural formula III is generated after the reaction is carried out for a certain time;
wherein in the formula I, R1, R2, R3 and X are F or Cl simultaneously; or R1, R2 and X are F or Cl simultaneously, and R3 is H; in the formula II, R4 is methyl or ethyl. The compound of formula I is difluoroacetyl fluoride or trifluoroacetyl fluoride or dichloroacetyl chloride or trichloroacetyl chloride. The compound of formula II is a methoxyacrylate or an ethoxyacrylate.
The temperature of the first reaction stage is designed to be-30-0 ℃, and the reaction is safe and reliable in the low-temperature range, controllable and high in reaction selectivity. The second stage reaction temperature is designed to be 0-50 ℃ because after reactants react for a period of time at low temperature, the concentration of the affected substances is reduced, the products are increased, the reaction rate is sharply reduced, and the temperature is increased to be beneficial to the forward reaction.
In one embodiment of the invention, the molar ratio of the compound with the chemical structural formula I to the acid-binding agent is 1: 1-1.5.
In one embodiment of the present invention, the ratio of compounds I and II is 1: 0.5-5.
In one embodiment of the present invention, the ratio of the organic solvent to the amount of the compound of formula I is 1-10: 1.
In one embodiment of the present invention, the ratio of the amount of the organic solvent to the amount of the compound of formula I is 3: 1.
In one embodiment of the present invention, the reaction time of the second stage is 0.5-2 h.
In one embodiment of the present invention, the reaction time of the first stage is 1h, and the reaction time of the second stage is 1-2 h.
In one embodiment of the present invention, the compound with chemical structural formula II is dissolved in an organic solvent, the temperature is reduced to-10 ℃ for the first stage reaction, and then the temperature is increased to 10-15 ℃ for the second stage reaction.
The first reaction stage is more preferably-10 ℃, because the generated halide cannot react with an acid-binding agent in time after the reaction is lower than-10 ℃, so that the reaction effect is poor; and above-10 ℃, the reaction selectivity becomes poor and the yield of the target intermediate is reduced. The reaction temperature in the second reaction stage is more preferably 10 ℃ to 15 ℃ because in this temperature range, the preferred acid-binding agent in combination with the hydrogen halide salt is a liquid insoluble in the reaction solvent, has good fluidity, and is easy to separate. Meanwhile, an excessively high reaction temperature may cause partial dissociation of the target intermediate in the solvent, resulting in dual reduction of yield and selectivity.
In an embodiment of the present invention, the organic solvent is toluene, xylene, dichloromethane, or 1, 2-dichloroethane.
In an embodiment of the present invention, the acid-binding agent is an acid-binding agent with a long carbon chain, wherein the length of the carbon chain is greater than or equal to 8. The reactivity between the alkoxyacrylate and the haloacetyl halide can be greatly increased by using trihexyl (tetradecyl) phosphonium hydroxide or trimethyl (tetradecyl) ammonium hydroxide with an appropriate carbon chain to facilitate the obtainment of the target product.
The technical scheme has the following beneficial effects:
the method has the advantages of simple reaction route, mild reaction conditions, safe and controllable reaction process and high atom economy, and the target compound with high yield can be obtained at low temperature and normal pressure. The reaction is a replacement reaction, except hydrogen halide generated by the reaction, no other reaction product exists, the atom efficiency is high, the yield of the target compound is high, and the cost is reduced.
Compared with the existing preparation method of triethyl orthoformate with high price, the method has the advantage of reducing the cost. Meanwhile, the yield of the target intermediate is improved by using the acid-binding agent with long carbon chain; and the salt obtained by combining the acid-binding agent with the hydrogen halide is liquid, and the liquid is insoluble in the reaction liquid, is easy to separate and can be recycled.
Detailed Description
The present invention will be further described with reference to the following examples.
The 2-polyhalogenated acetyl-3-alkoxy acrylate with the structural formula III is prepared by taking alkoxy acrylate as a raw material and carrying out chemical reaction with a compound with the structural formula I in an organic solvent, wherein the structural formula II is shown in the specification. The reaction formula is as follows:
the reaction can effectively reduce the production cost and obtain the high-yield 2-polyhalogenated acetyl-3-alkoxy acrylate, and the reaction route has reasonable process, mild reaction conditions, easily controlled reaction process and better industrial value.
Comparative example 1
Adding 31.7g (0.22mol) of ethyl ethoxyacrylate and 55g (0.60mol) of toluene into a reaction bottle at normal temperature, stirring and cooling to-10 ℃, keeping the temperature, slowly dropwise adding 19.6g (0.20mol) of difluoroacetyl fluoride into the reaction bottle, stirring and reacting for 1 hour, heating to 10 ℃, stirring and reacting for 1 hour at the temperature, layering, and taking a supernatant to obtain the compound shown in the formula III (R1 and R2 are F, R3 are H, and R4 is ethyl).
Example 1
Adding 31.7g (0.22mol) of ethyl ethoxyacrylate into a reaction bottle at normal temperature, keeping the amount of an acid-binding agent substance at 0.20mol, changing the type of the acid-binding agent, adding 55g (0.60mol) of toluene, stirring and cooling to-10 ℃, keeping the temperature, slowly dropwise adding 19.6g (0.20mol) of difluoroacetyl fluoride into the reaction bottle, stirring and reacting for 1 hour, heating to 10 ℃, stirring and reacting for 1 hour at the temperature, layering, and taking a supernatant to obtain the compound shown in the formula III (R1, R2 are F, R3 are H, and R4 is ethyl).
The kinds of acid-binding agents used in comparative example 1 and the yields corresponding to 2-polyhaloacetyl-3-alkoxyacrylates are shown in Table 1.
TABLE 1
| Acid-binding agent species | Yield of objective product (%) |
| Acid-binding-free agent | 8.9 |
| Triethylamine | 34.8 |
| Pyridine compound | 43.8 |
| Trihexyl (tetradecyl) phosphonium hydroxide | 90.2 |
| Trimethyl (tetradecyl) ammonium hydroxide | 86.7 |
The reaction activity of the alkoxy acrylic ester and the halogenated acetyl halide can be completely excited by using a novel acid-binding agent. The use of common acid-binding agents such as triethylamine, tripropylamine, tributylamine, pyridine and the like cannot achieve good yield. The novel acid-binding agent has a longer carbon chain, so that the alkoxy acrylate and the halogenated acetyl halide are easy to effectively collide under the action of the acid-binding agent, and the reaction activity is increased. Meanwhile, the generated hydrogen halide salt is not dissolved in the reaction system and can be quickly separated from the system to promote the forward reaction.
Example 2
Adding 31.7g (0.22mol) of ethyl ethoxyacrylate into a reaction bottle at normal temperature, proportionally adding trihexyl (tetradecyl) phosphorus hydroxide and 55g (0.60mol) of toluene in different amounts, stirring and cooling to-10 ℃ while maintaining the temperature, slowly dropwise adding 19.6g (0.20mol) of difluoroacetylfluoride into the reaction bottle, stirring and reacting for 1 hour at the temperature, heating to 10 ℃, stirring and reacting for 1 hour, layering, and taking a supernatant to obtain the compound shown in the formula III (R1, R2 are F, R3 are H, and R4 are ethyl). In this example, the yields corresponding to the 2-polyhaloacetyl-3-alkoxyacrylate obtained when trihexyl (tetradecyl) phosphonium hydroxide was added in different amounts are shown in Table 2.
TABLE 2
Example 3
Adding 31.7g (0.22mol) of ethyl ethoxyacrylate into a reaction bottle at normal temperature, adding 110.11g (0.22mol) of trihexyl (tetradecyl) phosphorus hydroxide and 55g (0.60mol) of toluene, reducing the temperature to T1, slowly dropwise adding 19.6g (0.20mol) of difluoroacetylfluoride into the reaction bottle, stirring for reaction for 1 hour, heating to T2, stirring for reaction for 1 hour at the temperature, carrying out layering, and taking a supernatant to obtain the compound shown in the formula III (R1, R2 are F, R3 are H, and R4 are ethyl). In this example, the yields of 2-polyhaloacetyl-3-alkoxyacrylates obtained at different reaction temperatures are shown in Table 3.
TABLE 3
| T1(℃) | T2(℃) | Yield of objective product (%) |
| -30 | 10 | 73.3 |
| -20 | 10 | 88.7 |
| -15 | 10 | 93.2 |
| -0 | 10 | 89.5 |
| -10 | 0 | 93.2 |
| -10 | 10 | 97.8 |
| -10 | 15 | 91.6 |
| -10 | 30 | 80.7 |
| -10 | 50 | 69.4 |
Example 4
31.7g (0.22mol) of ethyl ethoxyacrylate was charged into a reaction flask at room temperature, 110.11g (0.22mol) of trihexyl (tetradecyl) phosphonium hydroxide and 92g (0.60mol) of toluene were charged into the flask, the mixture was stirred and cooled to-10 ℃ and kept at the temperature, 19.6g (0.20mol) of difluoroacetylfluoride was slowly dropped into the flask to react for 1 hour, the temperature was raised to 10 ℃ and the reaction was stirred at the temperature for 0.5 hour to conduct layering, and the supernatant was collected to obtain 41.8g of the compound represented by formula III (R1, R2 were F, R3 was H, and R4 was ethyl) in a yield of 94.1%.
Example 5
31.7g (0.22mol) of ethyl ethoxyacrylate was charged into a reaction flask at room temperature, 110.11g (0.22mol) of trihexyl (tetradecyl) phosphonium hydroxide and 55g (0.6mol) of toluene were charged into the flask, the mixture was stirred and cooled to-10 ℃ and kept at the temperature, 19.6g (0.20mol) of difluoroacetylfluoride was slowly dropped into the flask, the reaction was carried out for 4 hours, the temperature was raised to 10 ℃ and the reaction was carried out for 2 hours under stirring at the temperature, and then layers were separated, and the supernatant was taken to obtain 43.2g of the compound represented by formula III (R1, R2 are F, R3 are H, and R4 is ethyl), with a yield of 95.1%.
Example 6
Adding 31.7g (0.22mol) of ethyl ethoxyacrylate into a reaction bottle at normal temperature, adding 110.11g (0.22mol) of trihexyl (tetradecyl) phosphorus hydroxide and 63.6g (0.60mol) of xylene, reducing the temperature to-10 ℃, slowly adding difluoroacetylfluoride into the compound I and the compound II according to the amount ratio of different substances into the reaction bottle, stirring and reacting for 1 hour, heating to 10 ℃, stirring and reacting for 1 hour, layering, and taking supernatant to obtain the compound shown in the formula III (R1, R2 are F, R3 are H, and R4 is ethyl). In this example, the yields of 2-polyhaloacetyl-3-alkoxyacrylate obtained when the mass ratio of compound I to compound II was different are shown in Table 4.
TABLE 4
| Compound I/Compound II | Yield of objective product (%) |
| 1:0.5 | 45.2 |
| 1:1.0 | 95.3 |
| 1:1.1 | 97.8 |
| 1:1.3 | 97.9 |
| 1:2.0 | 97.7 |
| 1:5.0 | 97.9 |
The following examples were obtained by varying the groups of compound I and compound II:
example 7
Adding 31.7g (0.22mol) of ethyl ethoxyacrylate into a reaction bottle at normal temperature, adding 110.11g (0.22mol) of trihexyl (tetradecyl) phosphorus hydroxide and 55g (0.6mol) of toluene, reducing the temperature to-10 ℃, slowly dropwise adding 23.2g (0.20mol) of trifluoroacetyl fluoride into the reaction bottle while keeping the temperature, stirring for reaction for 1 hour, heating to 10 ℃, stirring for reaction for 1 hour at the temperature, layering, and taking supernatant to obtain 47.5g of a compound shown in the formula III (R1, R2 and R3 are F, and R4 is ethyl), wherein the yield is 99.0%;
example 8
Adding 25.5g (0.22mol) of methyl methoxyacrylate into a reaction bottle at normal temperature, adding 110.11g (0.22mol) of trihexyl (tetradecyl) phosphorus hydroxide and 55g (0.6mol) of toluene, reducing the temperature to-10 ℃, slowly dropwise adding 19.6g (0.20mol) of difluoroacetylfluoride into the reaction bottle while keeping the temperature, stirring for reaction for 1 hour, heating to 10 ℃, stirring for reaction for 1 hour at the temperature, layering, taking supernatant to obtain 37.6g of the compound shown in the formula III (R1, R2 are F, R3 are H, R4 is methyl), and the yield is 97.0%;
example 9
Adding 25.5g (0.22mol) of methyl methoxyacrylate into a reaction bottle at normal temperature, adding 110.11g (0.22mol) of trihexyl (tetradecyl) phosphorus hydroxide and 55g (0.6mol) of toluene, reducing the temperature to-10 ℃, slowly dropwise adding 23.2g (0.20mol) of trifluoroacetyl fluoride into the reaction bottle while keeping the temperature, stirring for reaction for 1 hour, heating to 10 ℃, stirring for reaction for 1 hour at the temperature, layering, and taking supernatant to obtain 41.6g of a compound shown in a formula III (R1, R2 and R3 are F, R4 is methyl), wherein the yield is 98.1%;
example 10
Adding 31.7g (0.22mol) of ethyl ethoxyacrylate into a reaction bottle at normal temperature, adding 110.11g (0.22mol) of trihexyl (tetradecyl) phosphorus hydroxide and 55g (0.6mol) of toluene, stirring and cooling to-10 ℃, slowly dropwise adding 32.2g (0.20mol) of dichloroacetyl chloride into the reaction bottle while keeping the temperature, stirring and reacting for 1 hour, heating to 10 ℃, stirring and reacting for 1 hour at the temperature, layering, and taking a supernatant to obtain 49.3g of the compound shown in the formula III (R1, R2 are Cl, R3 are H, R4 is ethyl), wherein the yield is 96.8%
Example 11
Adding 31.7g (0.22mol) of ethyl ethoxyacrylate into a reaction bottle at normal temperature, adding 110.11g (0.22mol) of trihexyl (tetradecyl) phosphorus hydroxide and 55g (0.6mol) of toluene, stirring and cooling to-10 ℃, keeping the temperature, slowly dropwise adding 36.3(0.20mol) of trichloroacetyl chloride into the reaction bottle, stirring and reacting for 1 hour, heating to 10 ℃, stirring and reacting for 1 hour at the temperature, layering, taking supernatant to obtain 56.3g of the compound shown in the formula III (R1, R2 and R3 are Cl and R4 is ethyl), wherein the yield is 97.3%;
example 12
Adding 25.5g (0.22mol) of methyl methoxyacrylate into a reaction bottle at normal temperature, adding 110.11g (0.22mol) of trihexyl (tetradecyl) phosphorus hydroxide and 55g (0.6mol) of toluene, stirring and cooling to-10 ℃, slowly dropwise adding 32.2g (0.20mol) of dichloroacetyl chloride into the reaction bottle while keeping the temperature, stirring and reacting for 1 hour, heating to 10 ℃, stirring and reacting for 1 hour at the temperature, layering, and taking a supernatant to obtain 44.2g of the compound shown in the formula III (R1, R2 are Cl, R3 are H, R4 is methyl), wherein the yield is 97.5%;
example 13
25.5g (0.22mol) of methyl methoxyacrylate was charged into a reaction flask at room temperature, 110.11g (0.22mol) of trihexyl (tetradecyl) phosphonium hydroxide and 55g (0.6mol) of toluene were charged into the flask, the mixture was stirred and cooled to-10 ℃ and kept at this temperature, 36.3(0.20mol) of trichloroacetyl chloride was slowly dropped into the flask, the mixture was stirred and reacted for 1 hour, the temperature was raised to 10 ℃ and stirred and reacted for 1 hour, and the mixture was separated into layers, and the supernatant was collected to obtain 51.2g of the compound represented by formula III (R1, R2, R3 were Cl, and R4 was methyl) in a yield of 97.9%.
The above-described embodiments are intended to illustrate rather than to limit the invention, and any changes and alterations made without inventive step within the spirit and scope of the claims are intended to fall within the scope of the invention.
Claims (10)
1. A preparation method of 2-polyhalogenated acetyl-3-alkoxy acrylic ester is characterized in that a compound with a chemical structural formula II is dissolved in an organic solvent, the temperature is reduced to minus 30 ℃ to 0 ℃, the compound with the chemical structural formula I is dripped under the action of an acid-binding agent to carry out a first-stage reaction for 0.5 to 4 hours, then the temperature is raised to 0 to 50 ℃, a second-stage reaction is carried out, and the 2-polyhalogenated acetyl-3-alkoxy acrylic ester with the chemical structural formula III is generated after the reaction is carried out for a certain time;
wherein in the formula I, R1, R2, R3 and X are F or Cl simultaneously; or R1, R2 and X are F or Cl simultaneously, and R3 is H; in the formula II, R4 is methyl or ethyl.
2. The method for preparing 2-polyhaloacetyl-3-alkoxy acrylate according to claim 1, wherein the molar ratio of the compound represented by the formula I to the acid-binding agent is 1: 1-1.5.
3. The process for the preparation of 2-polyhaloacetyl-3-alkoxyacrylates according to claim 1 wherein the ratio of compounds I to II is 1: 0.5-5.
4. The method for preparing 2-polyhaloacetyl-3-alkoxy acrylate according to claim 1, wherein the ratio of the amount of the organic solvent to the amount of the compound of formula I is 1-10: 1.
5. The method for preparing 2-polyhaloacetyl-3-alkoxy acrylate according to claim 4, wherein the mass ratio of the organic solvent to the compound of formula I is 3: 1.
6. The method for preparing 2-polyhaloacetyl-3-alkoxy acrylate according to claim 1 wherein the reaction time of the second stage is 0.5-2 hours.
7. The method for preparing 2-polyhaloacetyl-3-alkoxy acrylate according to claim 6, wherein the reaction time of the first stage is 1 hour and the reaction time of the second stage is 1 to 2 hours.
8. The method for preparing 2-polyhaloacetyl-3-alkoxy acrylate according to claim 1, wherein the compound of formula II is dissolved in an organic solvent, the temperature is reduced to-10 ℃ for the first stage reaction, and then the temperature is increased to 10 ℃ to 15 ℃ for the second stage reaction.
9. The process for preparing 2-polyhaloacetyl-3-alkoxyacrylates according to any one of claims 1 to 8, wherein the organic solvent is toluene, xylene, dichloromethane, 1, 2-dichloroethane.
10. The method for preparing 2-polyhaloacetyl-3-alkoxy acrylate according to claim 9, wherein the acid-binding agent is an acid-binding agent with a long carbon chain, wherein the length of the carbon chain is not less than 8.
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Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060252944A1 (en) * | 2003-10-23 | 2006-11-09 | Reinhard Lantzsch | Method for producing 2-dihaloacyl-3-amino-acrylic acid esters and 3-dihalomethyl pyrazole-4-carboxylic acid esters |
| CN101535274A (en) * | 2006-11-03 | 2009-09-16 | 巴斯夫欧洲公司 | Process for preparing difluoromethylpyrazolyl carboxylates |
| US20110004002A1 (en) * | 2008-02-29 | 2011-01-06 | Basf Se | Process for preparing alkyl 2-alkoxymethylene-4,4-difluoro-3-oxobutyrates |
| CN106467492A (en) * | 2015-08-14 | 2017-03-01 | 联化科技(盐城)有限公司 | The preparation method of polyfluoro methyl pyrazoles compound, intermediate and preparation method |
| CN110577503A (en) * | 2019-08-02 | 2019-12-17 | 宿迁市科莱博生物化学有限公司 | halogen substituted compound and preparation method and application thereof |
-
2019
- 2019-12-30 CN CN201911392168.0A patent/CN111116364B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20060252944A1 (en) * | 2003-10-23 | 2006-11-09 | Reinhard Lantzsch | Method for producing 2-dihaloacyl-3-amino-acrylic acid esters and 3-dihalomethyl pyrazole-4-carboxylic acid esters |
| CN101535274A (en) * | 2006-11-03 | 2009-09-16 | 巴斯夫欧洲公司 | Process for preparing difluoromethylpyrazolyl carboxylates |
| US20110004002A1 (en) * | 2008-02-29 | 2011-01-06 | Basf Se | Process for preparing alkyl 2-alkoxymethylene-4,4-difluoro-3-oxobutyrates |
| CN106467492A (en) * | 2015-08-14 | 2017-03-01 | 联化科技(盐城)有限公司 | The preparation method of polyfluoro methyl pyrazoles compound, intermediate and preparation method |
| CN110577503A (en) * | 2019-08-02 | 2019-12-17 | 宿迁市科莱博生物化学有限公司 | halogen substituted compound and preparation method and application thereof |
Non-Patent Citations (2)
| Title |
|---|
| MASAYOSHI MIYAGAWA 等: "Discovery of novel 5-hydroxy-4-pyridone-3-carboxy acids as potent inhibitors of influenza Cap-dependent endonuclease", 《BIOORGANIC & MEDICINAL CHEMISTRY LETTERS》 * |
| 鲍志远 等: "1-取代苯基-5-三氟甲基(二氟甲基)-4-吡唑甲酸的合成研究", 《化学试剂》 * |
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