2965-90-4

Usage

Uses

Used in Pharmaceutical Industry:
Diethyl 4-fluorophenyl malonate is used as an intermediate in the synthesis of pharmaceuticals for its ability to enhance the biological activity and metabolic stability of the resulting compounds. The incorporation of the 4-fluorophenyl group can improve the pharmacokinetic and pharmacodynamic properties of drug candidates, leading to more effective treatments.
Used in Agrochemical Industry:
In the agrochemical industry, Diethyl 4-fluorophenyl malonate serves as an intermediate in the synthesis of various agrochemicals. Its fluorinated structure can contribute to the development of more effective and environmentally friendly pesticides and herbicides.
Used in Organic Chemistry Research and Development:
Diethyl 4-fluorophenyl malonate is utilized in research and development studies in the field of organic chemistry. Its unique structure and properties make it a valuable compound for exploring new reaction pathways, synthesis methods, and the creation of novel organic compounds with potential applications in various industries.

InChI:InChI=1/C13H15FO4/c1-3-17-12(15)11(13(16)18-4-2)9-5-7-10(14)8-6-9/h5-8,11H,3-4H2,1-2H3

Upstream product

• 460-00-4 1-Bromo-4-fluorobenzene 
• 105-53-3 diethyl malonate 
• 352-34-1 4-fluoro-1-iodobenzene 
• 105-58-8 Diethyl carbonate 
• 587-88-2 ethyl 2-(4-fluorophenyl)acetate 
• 448-59-9 tris(4-fluorophenyl)boroxine 
• 405-50-5 p-Fluorophenylacetic acid 
• 459-04-1 4-Fluorophenylacetyl chloride 
• 623-49-4 ethyl cyanoformate 

Downstream Products

• 204201-52-5 2-(4-fluorophenyl)propane-1,3-diol 
• 1619918-11-4 diethyl 3-(4-fluorophenyl)cyclobutane-1,1-dicarboxylate 
• 1600566-87-7 C₂₉H₁₈F₄N₆O 
• 1600566-88-8 C₂₉H₁₈F₄N₆O 
• 1600566-85-5 3-(4-fluorophenyl)-6-(hydroxy(1-methyl-1H-imidazol-5-yl)(6-(trifluoromethyl)pyridin-3-yl)methyl)-8-methylquinoline-2,4-dicarbonitrile 
• 1600566-86-6 (2,4-dichloro-3-(4-fluorophenyl)-8-methylquinolin-6-yl)(1-methyl-1H-imidazol-5-yl)(6-(trifluoromethyl)pyridin-3-yl)methanol 
• 1600563-35-6 6-bromo-2,4-dichloro-3-(4-fluorophenyl)-8-methylquinoline 

Relevant academic research and scientific papers

Enantioselective Desymmetrization of 2-Aryl-1,3-propanediols by Direct O-Alkylation with a Rationally Designed Chiral Hemiboronic Acid Catalyst That Mitigates Substrate Conformational Poisoning

Enantioselective desymmetrization by direct monofunctionalization of prochiral diols is a powerful strategy to prepare valuable synthetic intermediates in high optical purity. Boron acids can activate diols toward nucleophilic additions; however, the design of stable chiral catalysts remains a challenge and highlights the need to identify new chemotypes for this purpose. Herein, the discovery and optimization of a bench-stable chiral 9-hydroxy-9,10-boroxarophenanthrene catalyst is described and applied in the highly enantioselective desymmetrization of 2-aryl-1,3-diols using benzylic electrophiles under operationally simple, ambient conditions. Nucleophilic activation and discrimination of the enantiotopic hydroxy groups on the diol substrate occurs via a defined chairlike six-membered anionic complex with the hemiboronic heterocycle. The optimal binaphthyl-based catalyst 1g features a large aryloxytrityl group to effectively shield one of the two prochiral hydroxy groups on the diol complex, whereas a strategically placed "methyl blocker"on the boroxarophenanthrene unit mitigates the deleterious effect of a competing conformation of the complexed diol that compromised the overall efficiency of the desymmetrization process. This methodology affords monoalkylated products in enantiomeric ratios equal or over 95:5 for a wide range of 1,3-propanediols with various 2-aryl/heteroaryl groups.

Radical Addition Enables 1,2-Aryl Migration from a Vinyl-Substituted All-Carbon Quaternary Center

An efficient method for photocatalytic perfluoroalkylation of vinyl-substituted all-carbon quaternary centers involving 1,2-aryl migration has been developed. The rearrangement reactions use fac-Ir(ppy)3, visible light and commercially available fluoroalkyl halides and can generate valuable multisubstituted perfluoroalkylated compounds in a single step that would be challenging to prepare by other methods. Mechanistically, the photoinduced alkyl radical addition to an alkene leads to the migration of a vicinal aryl substituent from its adjacent all-carbon quaternary center with the concomitant generation of a C-radical bearing two electron-withdrawing groups that is further reduced by a hydrogen donor to complete the domino sequence.

Evaluation of the Structure-Activity Relationship of Microtubule-Targeting 1,2,4-Triazolo[1,5- a]pyrimidines Identifies New Candidates for Neurodegenerative Tauopathies

Studies in tau and Aβ plaque transgenic mouse models demonstrated that brain-penetrant microtubule (MT)-stabilizing compounds, including the 1,2,4-triazolo[1,5-a]pyrimidines, hold promise as candidate treatments for Alzheimer's disease and related neurodegenerative tauopathies. Triazolopyrimidines have already been investigated as anticancer agents; however, the antimitotic activity of these compounds does not always correlate with stabilization of MTs in cells. Indeed, previous studies from our laboratories identified a critical role for the fragment linked at C6 in determining whether triazolopyrimidines promote MT stabilization or, conversely, disrupt MT integrity in cells. To further elucidate the structure-activity relationship (SAR) and to identify potentially improved MT-stabilizing candidates for neurodegenerative disease, a comprehensive set of 68 triazolopyrimidine congeners bearing structural modifications at C6 and/or C7 was designed, synthesized, and evaluated. These studies expand upon prior understanding of triazolopyrimidine SAR and enabled the identification of novel analogues that, relative to the existing lead, exhibit improved physicochemical properties, MT-stabilizing activity, and pharmacokinetics.

OXIDATIVE COUPLING OF ARYL BORON REAGENTS WITH SP3-CARBON NUCLEOPHILES, AND AMBIENT DECARBOXYLATIVE ARYLATION OF MALONATE HALF-ESTERS VIA OXIDATIVE CATALYSIS

Described herein are methods of oxidative coupling of aryl boron reagents with sp3-carbon nucleophiles, and ambient decarboxylative arylation of malonate half-esters via oxidative catalysis.

Palladium-Catalyzed Asymmetric Allylic Alkylation of 4-Substituted Isoxazolidin-5-ones: Straightforward Access to β2,2-Amino Acids

We report here an unprecedented and highly enantioselective palladium-catalyzed allylic alkylation applied to 4-substituted isoxazolidin-5-ones. Ultimately, the process provides a straightforward access to β2,2-amino acids bearing an all-carbon quaternary stereogenic center in great yields and a high degree of enantioselectivity.

Oxidative Coupling of Aryl Boron Reagents with sp3-Carbon Nucleophiles: the Enolate Chan-Evans-Lam Reaction

Reported is a versatile new oxidative method for the arylation of activated methylene species. Under mild reaction conditions (RT to 40 C), Cu(OTf)2 mediates the selective coupling of functionalized aryl boron species with a variety of stabilized sp3-nucl

Oxidative coupling of aryl boron reagents with sp3-carbon nucleophiles: The enolate chan–evans–lam reaction

Reported is a versatile new oxidative method for the arylation of activated methylene species. Under mild reaction conditions (RT to 40°C), Cu(OTf)2mediates the selective coupling of functionalized aryl boron species with a variety of stabilized sp3-nucleophiles. Tertiary malonates and amido esters can be employed as substrates to generate quaternary centers. Complementing either traditional cross-coupling or SNAr protocols, the transformation is chemoselective in the presence of halogen electrophiles, including aryl bromides and iodides. Substrates bearing amide, sulfonyl, and phosphonyl groups, which are not amenable to coupling under mild Hurtley-type conditions, are suitable reaction partners.

Arylation of diethyl malonate and ethyl cyanoacetate catalyzed by palladium/di-tert-butylneopentylphosphine

α-Arylated carbonyl derivatives are important structural motifs in many natural products and pharmaceutically active compounds. Although arylation of simple monocarbonyl compounds is a well-established methodology, metal-catalyzed arylation of β-dicarbonyl derivatives is significantly more challenging. The ability of β-dicarbonyl anions to bind to palladium in a κ2-O,O mode, rather than the κ1-C-bound mode required for bond formation, often results in the deactivation of catalyst systems. The C-bound form of the enolate can be favored through the use of sterically demanding ligands. Herein, we report that the sterically demanding di-tert-butylneopentylphosphine (DTBNpP) ligand in combination with Pd(dba)2 provides an effective catalyst for the coupling of aryl bromides and chlorides with diethyl malonate. The Pd/DTBNpP system also catalyzes the coupling of aryl bromides with ethyl cyanoacetate.

HETEROARYL LINKED QUINOLINYL MODULATORS OF RORyt

The present invention comprises compounds of Formula I. wherein: R1, R2, R3, R4, R5, R6, R7, R8, and R9 are defined in the specification. The invention also comprises a method of treating or ameliorating a syndrome, disorder or disease, wherein said syndrome, disorder or disease is rheumatoid arthritis or psoriasis. The invention also comprises a method of modulating RORγt activity in a mammal by administration of a therapeutically effective amount of at least one compound of claim 1.

New efficient ligand-free, copper nanoparticle catalyzed coupling reactions of aryl halides with diethyl malonate to produce α-arylation of malonates

Recently synthesized copper nanoparticles (Cu NP) were used to catalyze coupling of aryl halides with diethyl malonates to produce α-aryl malonates. Synthetic conditions, including solvents, relative amounts of reactants, catalyst, and temperature, etc. h