6341-72-6

Usage

Uses

Used in Pharmaceutical Industry:
Alpha-Methyl-4-biphenylacetic acid is used as an active pharmaceutical ingredient (API) for its COX-2 selective inhibition properties, which can be beneficial in the development of anti-inflammatory and pain relief medications.
Used in Quality Control and Drug Purity Assessment:
As an identified impurity in Flurbiprofen, alpha-Methyl-4-biphenylacetic acid plays a role in the quality control and drug purity assessment processes within the pharmaceutical industry. Its presence is monitored to ensure the safety and efficacy of the final drug product.
Used in Research and Development:
Due to its COX-2 selective inhibition, alpha-Methyl-4-biphenylacetic acid is also utilized in research and development for the discovery of new drugs and therapies targeting inflammation and pain. Its study can contribute to a better understanding of the underlying mechanisms of these conditions and potentially lead to the development of more effective treatments.

Synthesis Reference(s)

Synthesis, p. 456, 1982 DOI: 10.1055/s-1982-29832

InChI:InChI=1/C15H14O2/c1-11(15(16)17)12-7-9-14(10-8-12)13-5-3-2-4-6-13/h2-11H,1H3,(H,16,17)

Upstream product

• 74647-99-7 Methyl 2-(4'-biphenylyl)propanoate 
• 6524-81-8 ethyl 2-([1,1'-biphenyl]-4-yl)propanoate 
• 34645-72-2 (RS)-2-(4'-iodophenyl)propanoic acid 
• 100-58-3 phenylmagnesium bromide 
• 5728-52-9 (4-biphenylyl)acetic acid 
• 74-88-4 methyl iodide 
• 124-38-9 carbon dioxide 
• 58114-03-7 4-(1-chloroethyl)-1,1′-biphenyl 
• 98-80-6 phenylboronic acid 
• 14062-23-8 4-biphenylylacetic acid ethyl ester 
• 108-86-1 bromobenzene 
• 83022-53-1 2-Hydroxy-4'-phenylpropiophenone dimethylacetal 
• 1115022-98-4 2-[1-(4-biphenylyl)ethyl]-5-methylfuran 
• 2350-89-2 p-vinylbiphenyl 

Downstream Products

• 6244-56-0 2-biphenyl-4-yl-propionic acid-(2-piperidino-ethyl ester) 
• 1000701-09-6 methyl 2,3,4-tri-O-acetyl-1-O-{(2R)-2-(4-biphenylyl)}propionyl-β-D-glucopyranuronate 
• 48170-23-6 2-([1,1'-biphenyl]-4-yl)-2-methylpropanoic acid 
• 92-91-1 biphenyl-4-acetaldehyde 

Relevant academic research and scientific papers

Site-Selective, Remote sp3 C?H Carboxylation Enabled by the Merger of Photoredox and Nickel Catalysis

A photoinduced carboxylation of alkyl halides with CO2 at remote sp3 C?H sites enabled by the merger of photoredox and Ni catalysis is described. This protocol features a predictable reactivity and site selectivity that can be modulated by the ligand backbone. Preliminary studies reinforce a rationale based on a dynamic displacement of the catalyst throughout the alkyl side chain.

Palladium catalyzed hydrodefluorination of fluoro-(hetero)arenes

Palladium catalyzed hydrodefluorination was developed for fine-tuning the properties of fluoro-(hetero)aromatic compounds. The robust reaction can be set up in air, requires only commercially available components, and tolerates a variety of heterocycles and functionalities relevant to drug discovery. Given the prevalence of fluorine incorporation around metabolic hotspots, the corresponding deuterodefluorination reaction may prove useful for converting fluorinated libraries to deuterated analogues to suppress the oxidative metabolism by kinetic isotope effects.

Photocarboxylation of Benzylic C-H Bonds

The carboxylation of sp3-hybridized C-H bonds with CO2 is a challenging transformation. Herein, we report a visible-light-mediated carboxylation of benzylic C-H bonds with CO2 into 2-arylpropionic acids under metal-free conditions. Photo-oxidized triisopropylsilanethiol was used as the hydrogen atom transfer catalyst to afford a benzylic radical that accepts an electron from the reduced form of 2,3,4,6-tetra(9H-carbazol-9-yl)-5-(1-phenylethyl)benzonitrile generated in situ. The resulting benzylic carbanion reacts with CO2 to generate the corresponding carboxylic acid after protonation. The reaction proceeded without the addition of any sacrificial electron donor, electron acceptor or stoichiometric additives. Moderate to good yields of the desired products were obtained in a broad substrate scope. Several drugs were successfully synthesized using the novel strategy.

Visible-Light-Driven External-Reductant-Free Cross-Electrophile Couplings of Tetraalkyl Ammonium Salts

Cross-electrophile couplings between two electrophiles are powerful and economic methods to generate C-C bonds in the presence of stoichiometric external reductants. Herein, we report a novel strategy to realize the first external-reductant-free cross-electrophile coupling via visible-light photoredox catalysis. A variety of tetraalkyl ammonium salts, bearing primary, secondary, and tertiary C-N bonds, undergo selective couplings with aldehydes/ketone and CO2. Notably, the in situ generated byproduct, trimethylamine, is efficiently utilized as the electron donor. Moreover, this protocol exhibits mild reaction conditions, low catalyst loading, broad substrate scope, good functional group tolerance, and facile scalability. Mechanistic studies indicate that benzyl radicals and anions might be generated as the key intermediates via photocatalysis, providing a new direction for cross-electrophile couplings.

Regioselectivity inversion tuned by iron(iii) salts in palladium-catalyzed carbonylations

Impactful regioselectivity control is crucial for cost-effective chemical synthesis. By using cheap and abundant iron(iii) salts, the hydroxycarbonylations of both aromatic and aliphatic alkenes were significantly enhanced in both reactivity and selectivity (iso/n or n/iso up to >99:1). Moreover, Pd-catalyzed carbonylation selectivity can be switched from branched to linear by using different Fe(iii) salts. In addition, similar results were obtained for the carbonylation of secondary alcohols.

Ligand-Controlled Regioselective Hydrocarboxylation of Styrenes with CO2 by Combining Visible Light and Nickel Catalysis

The ligand-controlled Markovnikov and anti-Markovnikov hydrocarboxylation of styrenes with atmospheric pressure of CO2 at room temperature using dual visible-light-nickel catalysis has been developed. In the presence of neocuproine as ligand, the Markovnikov product is obtained exclusively, while employing 1,4-bis(diphenylphosphino)butane (dppb) as the ligand favors the formation of the anti-Markovnikov product. A range of functional groups and electron-poor, -neutral, as well as electron-rich styrene derivatives are tolerated by the reaction, providing the desired products in moderate to good yields. Preliminary mechanistic investigations indicate the generation of a nickel hydride (H-NiII) intermediate, which subsequently adds irreversibly to styrenes.

A Ligand-Directed Catalytic Regioselective Hydrocarboxylation of Aryl Olefins with Pd and Formic Acid

An effective Pd-catalyzed hydrocarboxylation of aryl olefins with Ac2O and formic acid is described. A variety of 2- and 3-arylpropanoic acids can be regioselectively formed by the judicious choice of ligand without the use of toxic CO gas.

Nickel-Catalyzed Carboxylation of Benzylic C-N Bonds with CO2

A user-friendly Ni-catalyzed reductive carboxylation of benzylic C-N bonds with CO2 is described. This procedure outperforms state-of-the-art techniques for the carboxylation of benzyl electrophiles by avoiding commonly observed parasitic pathways, such as homodimerization or β-hydride elimination, thus leading to new knowledge in cross-electrophile reactions.

Decarboxylative fluorination of aliphatic carboxylic acids via photoredox catalysis

The direct conversion of aliphatic carboxylic acids to the corresponding alkyl fluorides has been achieved via visible light-promoted photoredox catalysis. This operationally simple, redox-neutral fluorination method is amenable to a wide variety of carboxylic acids. Photon-induced oxidation of carboxylates leads to the formation of carboxyl radicals, which upon rapid CO2-extrusion and F? transfer from a fluorinating reagent yield the desired fluoroalkanes with high efficiency. Experimental evidence indicates that an oxidative quenching pathway is operable in this broadly applicable fluorination protocol.