352-24-9

Usage

Uses

Used in Pharmaceutical Industry:
Ethyl 4,4-difluoro-3-oxobutanoate is used as a key intermediate for the synthesis of pharmaceuticals, specifically targeting the development of potassium channel activators and β-alanine derived GABA-T antagonists. Its unique difluoro substitution plays a significant role in enhancing the potency and selectivity of these drugs, making it an essential component in the pharmaceutical synthesis process.
In the development of potassium channel activators, Ethyl 4,4-difluoro-3-oxobutanoate contributes to the modulation of potassium channels, which are crucial for maintaining the electrical balance in cells. This can have therapeutic applications in treating conditions such as hypertension, cardiac arrhythmias, and other cardiovascular diseases.
For the synthesis of β-alanine derived GABA-T antagonists, Ethyl 4,4-difluoro-3-oxobutanoate is utilized to inhibit the enzyme GABA transaminase (GABA-T), which is responsible for the breakdown of the neurotransmitter gamma-aminobutyric acid (GABA). By inhibiting GABA-T, the levels of GABA in the brain can be increased, potentially providing therapeutic benefits for conditions such as epilepsy, anxiety, and other neurological disorders.
Overall, Ethyl 4,4-difluoro-3-oxobutanoate is a versatile and essential intermediate in the pharmaceutical industry, playing a critical role in the development of novel therapeutic agents for various medical conditions.

InChI:InChI=1/C6H8F2O3/c1-2-11-5(10)3-4(9)6(7)8/h6H,2-3H2,1H3

Upstream product

• 454-31-9 ethyl difluoroacetate 
• 141-78-6 ethyl acetate 
• 98-86-2 acetophenone 
• 367922-07-4 ethyl 4-bromo-4,4-difluoro-3-oxybutaneoate 
• 93-55-0 1-phenyl-propan-1-one 
• 100-06-1 1-(4-methoxyphenyl)ethanone 
• 433-53-4 difluoroacetic acid methyl ester 
• 1737-51-5 1-bromo-2-chloro-4,4-diethoxy-1,1,2-trifluoro-butane 
• 823234-80-6 ethyl 3-[(dimethoxyphosphoryl)oxy]-4,4-difluorobut-3-enoate 
• 667-50-5 Difluoroacetic acid N,N-dimethylamide 
• 124-41-4 sodium methylate 
• 686-11-3 N,N-diethyl-2,2-difluoroacetamide 
• 2063-17-4 4-chloro-4,4-difluoro-3-oxo-butyric acid ethyl ester 
• 1550-50-1 1,1,2,2-tetrafluoro-N,N-dimethylethan-1-amine 

Downstream Products

• 150618-33-0 ethyl 4,4-difluoro-3-benzylamino-2-butenoate 
• 37746-82-0 ethyl (E)-4,4-difluoro-but-2-enoate 
• 178381-06-1 4,4-Difluoro-3-{[1-phenyl-meth-(E)-ylidene]-amino}-butyric acid ethyl ester 
• 1086400-66-9 (Z)-2-(ethoxymethylene)-4,4-difluoro-3-oxobutanoic acid ethyl ester 
• 90185-24-3 Ethyl-4,4-difluoro-3-benzylamino 2-butenoate 
• 81982-54-9 Ethyl 4,4-difluoro 3-amino-2-butenoate 
• 81982-49-2 ethyl 3-(N-benzylamino)-4,4-difluorobutanoate 
• 129922-58-3 1-methyl-3-difluoromethyl-5-hydroxy-1H-pyrazole 
• 176969-33-8 (E/Z)-ethyl 2-(ethoxymethylene)-4,4-difluoro-3-oxobutanoate 
• 1253075-41-0 diethyl 2,6-bis(difluoromethyl)-4-(4-chloro-2-(trifluoromethyl)phenyl)-1,4-dihydropyridine-3,5-dicarboxylate 
• 1253075-35-2 diethyl 2,6-bis(difluoromethyl)-4-(3-cyanophenyl)-1,4-dihydropyridine-3,5-dicarboxylate 
• 1253075-39-6 diethyl 2,6-bis(difluoromethyl)-4-(2,3-difluorophenyl)-1,4-dihydropyridine-3,5-dicarboxylate 
• 1253075-27-2 diethyl 2,6-bis(difluoromethyl)-4-(4-methylphenyl)-1,4-dihydropyridine-3,5-dicarboxylate 
• 1253075-33-0 diethyl 2,6-bis(difluoromethyl)-4-(4-fluorophenyl)-1,4-dihydropyridine-3,5-dicarboxylate 

Relevant academic research and scientific papers

Synthesis of analogs of farnesyl diphosphate

Syntheses of analogs of farnesyl diphosphate (FPP) bearing substitutions at C3 are described. The mono-, di-, and trifluoromethylFPP derivatives were prepared by alkylation of appropriately substituted acetoacetates with geranyl bromide, followed by decarboxylation to obtain fluorinated ketones and a Wittig condensation to give the farnesyl skeleton. A similar sequence was used to synthesize 13-desmethylFPP.

Synthesis of fungicidally active succinate dehydrogenase inhibitors with novel difluoromethylated heterocyclic acid moieties

Abstract: Novel fungicidally active succinate dehydrogenase inhibitors have been prepared, which either carry a difluoromethyl and methyl-bearing pyrazoline, pyrrole, or thiophene ring in the acid component, mimicking similar-substituted pyrazole carboxamides. As five-membered heterocyclic systems with such a special substitution pattern are barely known, unique synthesis routes had to be developed, which rely, e.g., on the van Leusen pyrrole synthesis and the halogen dance reaction. Synthesis and biological activity against selected Ascomycete pathogens of these difluoromethylated pyrazoline, pyrrole, and thiophene derivatives are reported.

Design, Synthesis, and Pesticidal Activities of Pyrimidin-4-amine Derivatives Bearing a 5-(Trifluoromethyl)-1,2,4-oxadiazole Moiety

It is important to discover new pesticides with new modes of action because of the increasing evolution of pesticide resistance. In this study, a series of novel pyrimidin-4-amine derivatives containing a 5-(trifluoromethyl)-1,2,4-oxadiazole moiety were designed and synthesized. Their structures were confirmed by 1H NMR, 13C NMR, and HRMS. Bioassays indicated that the 29 compounds synthesized possessed excellent insecticidal activity against Mythimna separata, Aphis medicagini, and Tetranychus cinnabarinus and fungicidal activity against Pseudoperonospora cubensis. Among these pyrimidin-4-amine compounds, 5-chloro-N-(2-fluoro-4-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzyl)-6-(1-fluoroethyl)pyrimidin-4-amine (U7) and 5-bromo-N-(2-fluoro-4-(5-(trifluoromethyl)-1,2,4-oxadiazol-3-yl)benzyl)-6-(1-fluoroethyl) pyrimidin-4-amine(U8) had broad-spectrum insecticidal and fungicidal activity. The LC50 values were 3.57 ± 0.42, 4.22 ± 0.47, and 3.14 ± 0.73 mg/L for U7, U8, and flufenerim against M. separata, respectively. The EC50 values were 24.94 ± 2.13, 30.79 ± 2.21, and 3.18 ± 0.21 mg/L for U7, U8, and azoxystrobin against P. cubensis, respectively. The AChE enzymatic activity testing revealed that the enzyme activities of compounds U7, U8, and flufenerim are 0.215, 0.184, and 0.184 U/mg prot, respectively. The molecular docking results of compounds U7, U8, and flufenerim with the AChE model demonstrated the opposite docking mode between compound U7 or U8 and positive control flufenerim in the active site of AChE. The structure-activity relationships are also discussed. This work provided excellent pesticide for further optimization. Density functional theory analysis can potentially be used to design more active compounds.

Cu-Mediated Expeditious Annulation of Alkyl 3-Aminoacrylates with Aryldiazonium Salts: Access to Alkyl N2-Aryl 1,2,3-Triazole-carboxylates for Druglike Molecular Synthesis

Alkyl N-aryl 1,2,3-triazole-carboxylates are important molecules or intermediates in medicinal chemistry, but the synthesis of N2-aryl counterparts remains elusive. Herein, we describe a Cu-mediated annulation reaction of alkyl 3-aminoacrylates with aryldiazonium salts, both of which are readily available substrates. Furthermore, alkyl 2-aminoacrylates are also viable substrates. Diverse alkyl N2-aryl 1,2,3-triazole-carboxylates and their analogues can be rapidly prepared under mild conditions. Especially, this protocol allows one to access several druglike variants of carbonic anhydrase inhibitors and celecoxib.

INHIBITORS OF LEUCINE RICH REPEAT KINASE 2

The present invention relates to novel compounds that inhibit LRRK2 kinase activity, to processes for their preparation, to compositions containing them and to their use in the treatment of or prevention of diseases associated with or characterized by LRRK2 kinase activity, for example Parkinson's disease, Alzheimer's disease and amyotrophic lateral sclerosis (ALS).

A laminated material for catalytic synthesis of difluoro-acetyl-acetic acid ethyl ester

The invention discloses a method for synthesizing ethyl 4,4-difluoroacetoacetate in a catalyzed mode through layered materials. The method includes the following steps: 1, a divalent and trivalent metal salt solution and a sodium hydroxide and sodium carbonate mixed solution are rapidly mixed to prepare multielement hydrotalcite, the multielement hydrotalcite is roasted to be added into a fluoride-salt saturation aqueous solution, the mixture is stirred, filtered, washed and dried to be roasted under the nitrogen condition, and catalysts are obtained; 2, ethyl acetate, ethyl difluoroacetate and the catalysts are added into a four-opening flask, an ethyl alcohol and ethyl acetate mixture is evaporated after temperature rising, stirring and reacting are carried out, cooling is carried out, catalysts are filtered and recycled, filtrate is acidized, cooled and filtered, and pressure reduction rectification is carried out on the filtrate to obtain the ethyl 4,4-difluoroacetoacetate; 3, the recycled catalysts are sufficiently washed through solvents and roasted to be added into a fluoride-salt saturation aqueous solution, the mixture is stirred, filtered, washed and dried to be roasted under the nitrogen condition, and the catalysts are regenerated. The method has the advantages that the yield is high, the catalysts can be recycled, and the method is safe and environmentally friendly.

A 4, 4 - difluoro-acetyl-acetic acid alkyl ester preparation method

The invention discloses a method for preparing alkyl 4,4-difluoroacetylacetate. The method has the advantages of easily available raw materials, simple process flow, safety in operation and high yield. The method comprises the following steps: (1) carrying out hydrolysis reaction on 1,1,2,2-tetrafluoroethyl ether used as a raw material and water in an acid and separating to obtain ethyl difluoroacetate and hydrogen fluoride; (2) reacting ethyl difluoroacetate obtained in the step (1) and alkyl acetate in the presence of an alkaline catalyst to obtain 1,1-difluoro-2-butenoic acid alkyl ester-2-hydroxy salt; and (3) neutralizing 1,1-difluoro-2-butenoic acid alkyl ester-2-hydroxy salt obtained in the step (2) and hydrogen fluoride to obtain alkyl 4,4-difluoroacetylacetate.

SUBSTITUTED 3-AZABICYCLO[3.1.0]HEXANES AS KETOHEXOKINASE INHIBITORS

Provided herein are substituted 3-azabicyclo[3.1.0]hexanes as ketohexokinase inhibitors, processes to make said compounds, and methods comprising administering said compounds to a mammal in need thereof.

3-difluromethyl-1-methyl-pyrazole-4-formic acid and synthetic method thereof

The present invention relates to the field of chemical industry, and more specifically, relates to 3-difluromethyl-1-methyl-pyrazole-4-formic acid and a synthetic method thereof, the synthetic method comprises the steps: DFKE synthesis; DFVKE synthesis; DFPE synthesis; and DFPA synthesis. The synthesis method has the advantages of cheap and easily-obtained materials, greenness, environmental-friendliness, simple reaction conditions, less impurities and high yield, the prepared 3-difluromethyl-1-methyl-pyrazole-4-formic acid has high quality and high purity, and the yield is 90% or more.

Novel process for preparing 4,4-difluoro-((2-dialkylamino) methylene)-3-oxobutanic acid alkyl ester

The present invention relates to a novel method for preparing 4,4-difluoro-((2-dialkylamino) methylene)-3-oxobutanic acid alkyl ester which is represented by the following chemical formula ( I ) and useful as a manufacturing intermediate for fungicides such as isopyrazam, sedaxane, bixafen and the like. In the formula ( I ), R 1 and R 2 are each a C 1 to C 4 alkyl group, and R is a methyl group or an ethyl group. The compound of the formula ( I ) is produced by reacting dialkylformamide dialkyl acetal with a difluoro ketoester.