- Preparation method of 2, 4, 5-trifluorophenylacetic acid
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The invention provides a preparation method of 2, 4, 5-trifluorophenylacetic acid. The method comprises the following steps: 1) reacting 2, 4, 5-trifluorobromobenzene with metal magnesium to obtain 2, 4, 5-trifluorophenyl magnesium bromide; 2) reacting 2, 4, 5-trifluorophenyl magnesium bromide with halogenated acetate to prepare an intermediate A; 3) hydrolyzing the intermediate A in an alkaline solution or an acidic solution to obtain 2, 4, 5-trifluorophenylacetic acid. The structure of the intermediate A is shown as the following structure, wherein R represents a C1-C10 alkyl group. The preparation method of 2, 4, 5-trifluorophenylacetic acid provided by the invention has the advantages of simple process flow, low cost, environmental friendliness and mild conditions.
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Paragraph 0065-0067; 0071-0076; 0079-0080
(2021/07/28)
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- Industrial preparation method of 2,4,5-trifluorophenylacetic acid
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The invention relates to the technical field of preparation of chemical drug intermediates, and particularly discloses an industrial preparation method of 2,4,5-trifluorophenylacetic acid. The preparation method comprises the following steps: carrying out a nitration reaction, a fluorination reaction, a hydrogenation reduction reaction, a diazotization reaction, a halogenation reaction, a cyaniding reaction, a thermal decomposition reaction and a hydrolysis reaction on 2,4-dichlorotoluene to prepare the 2,4,5-trifluorophenylacetic acid. The method has the advantages of low preparation cost andhigh product yield.
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- Novel preparation method of 2, 4, 5-trifluorophenylacetic acid
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The invention discloses a novel preparation method of 2, 4, 5-trifluorophenylacetic acid, which belongs to the technical field of preparation of medical intermediates, and comprises the following preparation steps: carrying out nitration reaction on sulfuric acid and m-dichlorobenzene to obtain an intermediate II; adding the intermediate II, a phase transfer catalyst and potassium fluoride into an aprotic solvent to obtain an intermediate III; performing hydrogenation reaction on the intermediate III to obtain an intermediate IV; carrying out diazotization reaction on the intermediate IV, nitrosyl sulfuric acid and sodium fluoborate to obtain an intermediate V; performing cracking reaction on the intermediate V to obtain an intermediate VI; carrying out reduction reaction on the intermediate VI, and then carrying out bromination reaction on the intermediate VI and liquid bromine to obtain an intermediate VII; subjecting the intermediate VII to a substitution reaction with diethyl malonate, and obtaining 2, 4, 5-trifluorophenylacetic acid after hydrolysis and purification. A novel synthesis route is provided, the problem that technological operation is tedious is solved, the requirements for reaction and operation conditions are low, anhydrous and oxygen-free reaction conditions are not needed, the method is suitable for industrial production, and the yield and purity are greatly improved.
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Paragraph 0037; 0075; 0088-0089; 0097-0100; 0102-0103; ...
(2021/06/23)
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- Preparation method of 2,4,5-trifluorophenylacetic acid
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The invention belongs to the technical field of preparation of drug intermediates, and discloses a preparation method of 2,4,5-trifluorophenylacetic acid, wherein the preparation method comprises the steps: step 1, reacting raw materials, a quaternary ammonium salt catalyst, sulfolane and potassium fluoride to obtain a first intermediate; step 2, carrying out hydrogenation catalytic reaction on the first intermediate to obtain a second intermediate; step 3, carrying out salt forming reaction on the second intermediate and a fluorinating reagent, quenching, and carrying out diazotization reaction on the second intermediate and a sodium nitrite aqueous solution to obtain diazonium salt; step 4, carrying out high-temperature cracking on the diazonium salt, to obtain 2,4,5-trifluorotoluene; and step 5 to step 7, carrying out halogenation, cyanidation and hydrolysis reactions on 2,4,5-trifluorotoluene in sequence, and thus obtaining 2,4,5-trifluorophenylacetic acid. The raw materials adopted by the method are easy to obtain and low in cost, the yield of the corresponding product obtained in each step is high, and large-scale production of the 2,4,5-trifluorophenylacetic acid is facilitated.
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- Preparation method of 2,4,5-trifluorophenylacetic acid
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The invention provides a preparation method of 2,4,5-trifluorophenylacetic acid. 1,2,4-trifluorobenzene as a raw material and glycolide are catalyzed by a Lewis acid to obtain a final product that issitagliptin intermediate 2,4,5-trifluorophenylacetic acid. The method is mild in reaction condition, and convenient to operate, raw materials are cheap and easily available, steps are simple, and operability is high. High-pressure reaction equipment is not used in the production process, harmful and toxic reagents are not involved, the method has the advantages of being high in safety and environmentally friendly, the obtained 2,4,5-trifluorophenylacetic acid is high in purity, a more valuable synthetic route is provided for preparation of sitagliptin, good social benefits and economic benefits can be brought, and the economic value potential is large.
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Paragraph 0025; 0027-0028
(2020/07/21)
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- Synthesis method of sitagliptin intermediate 2,4,5-trifluorophenylacetic acid
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The present invention provides a synthesis method of a sitagliptin intermediate 2,4,5-trifluorophenylacetic acid. The method comprises a substitution reaction, a hydrolysis reaction and a decarboxylation reaction, and specifically comprises: A, carrying out a substitution reaction on a compound 4, or sequentially carrying out a substitution reaction and a hydrolysis reaction to prepare a compoundrepresented by a formula 5; B, carrying out a hydrolysis reaction on the compound represented by the formula 5 to prepare a compound represented by a formula 6; and C, carrying out a decarboxylation reaction on the compound represented by the formula 6 under the catalysis of a catalyst to prepare 2,4,5-trifluorophenylacetic acid, wherein the catalyst is a metal oxide. According to the synthesis process, the 2,4,5-trifluorophenylacetic acid compound is prepared with low cost and high yield, and the industrial scale-up production applicability is high.
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Paragraph 0145-0148
(2020/06/09)
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- Preparation method of 1,3-dicarbonyl compound and intermediate of the 1,3-dicarbonyl compound
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The invention discloses a preparation method of a 1,3-dicarbonyl compound and an intermediate of the 1,3-dicarbonyl compound, and particularly discloses a preparation method of a compound as shown ina formula I. The preparation method comprises the following step: in a solvent, performing an elimination reaction as shown in the specification on a compound as shown in a formula II to obtain the compound as shown in the formula I, wherein R is a tert-butoxy group, a methoxy group, an ethoxy group or a methyl group. The preparation method disclosed by the invention is relatively low in cost andbeneficial to industrial production.
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- Hydrogen Bond Directed Photocatalytic Hydrodefluorination and Methods of Use Thereof
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Methods of synthesizing compounds comprising fluorinated aryl groups are disclosed, wherein said methods utilize hydrogen bond directed photocatalytic hydrodefluorination.
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Paragraph 0138
(2021/01/22)
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- Synthesis method of 2,4,5-trifluorophenylacetic acid
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The invention discloses a synthesis method of 2,4,5-trifluorophenylacetic acid. 2,4,5-trifluorobromobenzene is used as starting material and condensed with diethyl malonate under the action of magnesium ethylate to obtain 2,4,5-trifluoro-diethyl malonate, 2,4,5-trifluoro-diethyl malonate is hydrolyzed under acidic conditions to obtain 2,4,5-trifluorophenylacetic acid. The invention is simple and easy to operate, the raw materials are cheap and easily available, the total reaction yield is high, and the invention is suitable for industrial production.
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Paragraph 0008-0009
(2020/01/12)
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- Synthesis method of sitagliptin intermediate 2,4,5-trifluorophenylacetic acid
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The invention discloses a synthesis method of sitagliptin intermediate 2,4,5-trifluorophenylacetic acid. The synthesis method comprises the following steps: reaction of 1,2,4-trifluoro-benzene with dichloromethane and cyanide under the action of a catalyst to obtain 2,4,5-trifluorophenylacetic acid. The method is simple in reaction operation, and after chloromethylation is completed, cyanation canbe directly carried out without post-treatment, the reaction yield is higher, the cost is lower, and the synthesis method is less in by-products and less in discharge of three wastes.
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Paragraph 0033-0086
(2019/10/01)
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- NEW EFFICIENT PROCESS FOR THE PREPARATION OF SITAGLIPTIN.
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Object of the present invention is an efficient process for the preparation of the active pharmaceutical ingredient Sitagliptine and the 2,4,5-trifluorophenylacetic acid (TFAA) and salt thereof, which is a key intermediate for the synthesis of Sitagliptine. (I)
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- 2. The preparation method of the 4, 5 - trifluorobenzene acetic acid
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The invention discloses a 2, 4, 5 - trifluorobenzene acetic acid preparation method, which belongs to the chemical pharmaceutical intermediates preparation method technical field, the use of 2, 4 - dichlorofluorobenzene as raw materials, by nitration, fluorinated, chlorinated, coupling and hydrolysis reaction for preparing 2, 4, 5 - trifluorobenzene acetic acid. The method of the invention, the raw materials using relatively inexpensive and easy to obtain, the process route is mature, the operation is simple, high yield, and has high industrial value.
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Paragraph 0039-0041
(2019/03/23)
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- EFFICIENT PROCESS FOR THE PREPARATION OF SITAGLIPTIN THROUGH A VERY EFFECTIVE PREPARATION OF THE INTERMEDIATE 2,4,5-TRIFLUOROPHENYLACETIC ACID
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Object of the present invention is an efficient process for the preparation of the active pharmaceutical ingredient Sitagliptine and the 2,4,5-trifluorophenylacetic acid (TFAA) and salt thereof, which is a key intermediate for the synthesis of Sitagliptine.
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Paragraph 00161; 00162; 00163; 00164; 00165
(2019/01/21)
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- A method for preparing 2, 4, 5 - trifluorobenzene acetic acid (by machine translation)
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The invention discloses a 2, 4, 5 - trifluorobenzene acetic acid. The method includes the steps of: (1) the structure shown as formula A 2, 4, 5 - trifluorobenzene diazonium salt with the structure shown in formula II substituted ethylene to carry out coupling reaction, to obtain the intermediate; and (2) the intermediate through hydrolysis or oxidation of the structure is shown as formula I shown in 2, 4, 5 - trifluorobenzene acetic acid; the intermediate comprises a structure of formula IV or a compound represented by the structure of formula C shown 2, 4, 5 - trifluoro phenylacetaldehydes. (by machine translation)
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Paragraph 0104-0106; 0108-0110; 0115-0117
(2018/12/03)
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- Preparation method of 2,4,5-trifluorophenylacetic acid
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The invention relates to a preparation method of 2,4,5-trifluorophenylacetic acid, belongs to the technical field of drug intermediate synthesizing, and aims to solve the problem that existing raw materials are high in risks. The method includes: allowing 2-methyl-4-nitrobenzoic acid to have reaction with nitrite under the effect of strong acid to generate diazotizing salt, adding hydrofluoric acid or fluoborate to perform fluorination, and performing pyrolysis to obtain a compound as shown in formula II; in the presence of an acid-binding agent, allowing the compound as shown in formula II tohave acylation reaction with halogenated acetyl chloride to obtain a compound as shown in formula III; under the effect of alkali metal alkoxide, allowing the compound as shown in formula III to havereaction with alcohol to obtain a compound as shown in formula IV; performing hydrolysis and decarboxylation on the compound as shown in formula IV in an acid system, performing reduction, and then performing diazotization and pyrolysis to obtain the 2,4,5-trifluorophenylacetic acid. The preparation method has the advantages that raw material conversion rate is increased, quality requirements onproduct yield and purity are satisfied, and high final-product total yield is achieved.
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Paragraph 0044; 0048; 0052; 0056; 0060
(2018/09/08)
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- Efficient preparation method of 2, 4, 5-trifluorophenylacetic acid
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The invention discloses an efficient preparation method of 2, 4, 5-trifluorophenylacetic acid and belongs to the technical field of synthesis of a pharmaceutical intermediate. The preparation method comprises synthesis of 2, 3, 5-trifluoroaniline, synthesis of 1, 2, 4-trifluorobenzene, synthesis of trifluorobromobenzene and synthesis of a desired product 2, 4, 5-trifluorophenylacetic acid. The preparation method is simple and easy to operate, utilizes cheap and easily available raw materials and has high reaction efficiency and good repeatability.
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Paragraph 0019
(2018/03/26)
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- Novel synthesis method of 2,4,5-trifluorophenylacetic acid
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The invention discloses a novel synthesis method of 2,4,5-trifluorophenylacetic acid and belongs to the technical field of synthesis of pharmaceutical intermediates. The novel synthesis method disclosed by the invention has a key point that: steps are shown in the description. The novel synthesis method disclosed by the invention has the advantages of simplicity and feasibility, cheap and easy-to-obtain raw materials, high reaction efficiency and good repeatability.
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- Novel method for preparing 2,4,5-trifluoro phenylacetic acid
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The invention provides a novel method for preparing 2,4,5-trifluoro-phenylacetic acid. The novel method specifically comprises the following steps: (1) dissolving 1,2,4-trifluoro benzene into 1,2-dihalogenated ethane, carrying out a Friedel-crafts alkylation reaction under catalysis of a lewis acid catalyst, thus preparing 2,4,5-trifluoro halogenated ethylbenzene; (2) hydrolyzing the 2,4,5-trifluoro halogenated ethylbenzene obtained in the step (1) in an alkaline system, thus obtaining 2,4,5-trifluoro phenethyl alcohol; (3) oxidizing the 2,4,5-trifluoro phenethyl alcohol obtained in the step (2), thus obtaining the 2,4,5-trifluoro phenylacetic acid. The novel method disclosed by the invention has the advantages that raw materials are easy to obtain, the reaction is mild, the operation is easy, the cost is low, environment friendliness is realized, no high-toxicity reagent exists, and the like.
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Paragraph 0048; 0049; 0050; 0051; 0052; 0053; 0054; 0055
(2017/08/29)
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- Preparation method of 2,4,5-trifluorophenylacetic acid
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The invention discloses a preparation method of 2,4,5-trifluorophenylacetic acid. The preparation method comprises the steps of carrying out a nucleophilic substitution reaction, a hydrolysis reaction and a decarboxylation reaction; the reaction equations are as follows, wherein R1 represents alkyl of C1-C12; R2 represents alkyl of C1-C6; R3 represents -CN or -COOR2, and R2 is the same as the above definition. The preparation method provided by the invention has the advantages of being simple in technology, low in cost, mild in reaction conditions, high in product purity and environmentally-friendly. The reaction equations (1)-(5) are described in the description.
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- Hydrogen Bond Directed Photocatalytic Hydrodefluorination: Overcoming Electronic Control
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The photocatalytic C-F functionalization of highly fluorinated arenes is a powerful method for accessing functionalized multifluorinated arenes. The decisive step in the determining regioselectivity in fluorine functionalization is fluoride fragmentation from the radical anion of the multifluorinated arene. To date, the availability of regioisomers has been dictated by the innate electronics of the fluorinated arene, limiting the synthetic utility of the chemistry. This study investigates the remarkable ability of a strategically located hydrogen bond to transcend the normal regioselectivity of the C-F functionalization event. A significant rate acceleration is additionally observed for hydrodefluorination of fluorines that can undergo intramolecular hydrogen bonds that form 5-8-membered cycles with moderately acidic N-H's. The hydrogen bond is expected to facilitate the fragmentation not only by bending the C-F bond of the radical anion out of planarity but also by increasing the exothermicity of the fluoride extrusion step through protonation of the naked fluoride. Finally, the synthetic utility of the method is demonstrated in an expedited synthesis of the trifluorinated α-phenyl acetic acid derivative required for the commercial synthesis of Januvia, an antidiabetic drug. This represents the first synthesis of a commercially important multifluorinated arene via a defluorination strategy and is significantly shorter than the current strategy.
- Khaled, Mohammad B.,El Mokadem, Roukaya K.,Weaver, Jimmie D.
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supporting information
p. 13092 - 13101
(2017/09/26)
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- Preparation method of fluorophenylacetic acid
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The invention relates to the field of chemical synthesis, and particularly relates to a preparation method of fluorophenylacetic acid. The invention provides a preparation method of fluorophenylacetic acid. The preparation method comprises the following steps: diazotization addition reaction: enabling a compound of the formula II to react in a system containing vinylidene chloride, acid, a diazonino reagent, a phase transfer catalyst and a copper catalyst to produce a compound of the formula III; and hydrolysis reaction: hydrolyzing the compound of the formula III to produce a compound of the formula I under the existence condition of acid. The preparation method is simply and easily available in raw materials, simple and convenient to operate, low in raw material cost, mild in reaction conditions, and low in danger, free from the use of high-price noble metal catalyst and complicated industrial operation means, and the quality of the product is stable, and therefore, the preparation method is suitable for industrial large-scale production.
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- A process for preparing 2, 4, 5-trifluorophenylacetic acid method
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The invention discloses a method for preparing 2,4,5-trifluorophenylacetic acid. The method is characterized by comprising the following steps: preparing 2,4,5-trifluorobromobenzene into a Grignard reagent, carrying out an addition reaction between the Grignard reagent and diethyl oxalate under the condition that a small amount of TMEDA is added, thereby preparing ethyl 2,4,5-trifluorobenzoylformate; carrying out reduction of ketone carbonyl and hydrolysis of an ester group on ethyl 2,4,5-trifluorobenzoylformate through a one-pot process under the action of hydrazine hydrate/potassium hydroxide (or sodium hydroxide)/diethylene glycol; and finally, acidizing to obtain the product. Compared with a conventional method for preparing 2,4,5-trifluorophenylacetic acid, the preparation method disclosed by the invention has the characteristics of cheap and readily available raw materials, high product yield, low production cost and fewer three wastes and has high industrial production value.
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Paragraph 0034; 0035
(2017/03/08)
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- A 2, 4, 5-trifluorophenylacetic acid method for the preparation of
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The invention discloses a preparation method 2,4,5-trifluorophenylacetic acid. The method is characterized by consisting of four reaction steps of: A, reaction of 2,4,5-trifluoronitrobenzene (I) and diethyl malonate which are condensed to prepare 2,5-difloro-4-nitrobenzophenone diethyl malonate; B, hydrolysis, acidification and decarboxylic reaction of dibasic ester; C, reduction reaction of nitryl; and D, diazotization fluoridation of amino. The four reaction steps can be sequentially carried out according to A, B, C and D, or A, C, B and D, or A, C, D and B. According to the preparation method provided by the invention, condensation of 2,4,5-trifluoronitrobenzene (I) and diethyl malonate is easy to realize by means of high substituting activity of nitryl p-fluorine, and the raw material 2,4,5-trifluoronitrobenzene (I) is low in cost and easy to obtain and can be easily prepared by nitration and fluorination of 2,4-dichlor fluorbenzene. Compared with the prior art, the preparation method provided by the invention has the characteristics of low-cost and easily obtained raw materials, mild reaction condition, high total yield, low production cost and the like, and is comparatively suitable for industrialized production.
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- NEW PROCESS FOR THE PREPARATION OF 2,4,5- TRIFLUOROPHENYLACETIC ACID"
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The present invention relates to a new process for the preparation of 2,4,5-trifluorophenylacetic acid and salts thereof by means of new synthetic intermediates.
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Paragraph 0057; 0058
(2014/03/24)
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- PROCESS FOR THE PREPARATION OF FLUOROPHENYLACETIC ACIDS AND DERIVATIVES THEREOF
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The object of the present invention is a process for the preparation of fluorophenylacetic acids and derivatives thereof, particularly of 2,4, 5-trifluorophenylacetic acid, starting from the corresponding mandelic acids.
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Page/Page column 18
(2008/12/06)
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- Process for the synthesis of trifluorophenylacetic acids
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The present invention addresses a process for the preparation of 2,4,5-trifluorophenylacetic acid using a Cu(I) salt as a catalyst.
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- Process for the synthesis of trifluorophenylacetic acids
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The present invention is concerned with a process for the preparation of trifluorophenylacetic acids using a Grignard reagent and an allylating agent, such as allyl bromide.
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