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Usage

Uses

Used in Pharmaceutical Industry:
(2S)-2-(4-Chlorophenyl)propanoic acid is used as an analgesic for the relief of mild to moderate pain, such as headaches, menstrual cramps, and musculoskeletal discomfort. It is effective due to its ability to inhibit the synthesis of prostaglandins, which are involved in the sensation of pain and inflammation.
Used in Anti-inflammatory Applications:
In the medical field, (2S)-2-(4-Chlorophenyl)propanoic acid serves as an anti-inflammatory agent, reducing inflammation associated with conditions like arthritis. Its mechanism of action involves the inhibition of cyclooxygenase (COX) enzymes, which are responsible for the production of prostaglandins that mediate inflammation.
Used in Antipyretic Therapy:
(2S)-2-(4-Chlorophenyl)propanoic acid is utilized as an antipyretic to reduce fever. It achieves this by acting on the hypothalamus to reset the body's temperature regulation, thereby lowering elevated body temperatures.
Used in Over-the-Counter Medications:
As a widely available over-the-counter medication, (2S)-2-(4-Chlorophenyl)propanoic acid is used for self-treatment of various conditions, including minor aches, pains, and fevers. Its accessibility and recognized safety profile when used as directed make it a popular choice for consumers seeking relief from common ailments.

Upstream product

• 2184-88-5 2-(4-chlorophenyl)propionitrile 
• 938-95-4 2-(4-Chloro-phenyl)-propionic acid 
• 62784-66-1 bis(1-naphthyl)methanol 
• 51747-43-4 2-(4-chlorophenyl)-acrylic acid 
• 1712-70-5 1-chloro-4-(1-methylethenyl)-benzene 
• 873-73-4 4-n-chlorophenylacetylene 
• 64-18-6 formic acid 
• 1073-67-2 4-vinylbenzyl chloride 
• 201230-82-2 carbon monoxide 
• 465529-75-3 tert-butyl 2-(4-chlorophenyl)propanoate 
• 286964-62-3 2-(4-chlorophenyl)propanal 
• 108-90-7 chlorobenzene 
• 1059200-71-3 (2'S,4R)-3-[2-(4-chlorophenyl)propionyl]-4-phenyloxazolidin-2-one 
• 130405-71-9 (±)-ethyl 2-(4-chlorophenyl)propanoate 

Downstream Products

• 1208553-06-3 C₁₂H₁₁ClN₂OS 
• 1095321-17-7 (S)-2-(3-fluorophenyl)propanoic acid 
• 10516-54-8 (R)-2-(4'-biphenylyl)propanoic acid 
• 137044-27-0 methyl (S)-2-(4-chlorophenyl)propanoate 
• 951016-04-9 (R)-methyl 2-(5-((S)-2-(4-chlorophenyl)propanamido)-1-oxoisoquinolin-2(1H)-yl)-3-methylbutanoate 
• 762300-23-2 (2S)-2-(4-chlorophenyl)-N-(3-{4-[5-(isobutyrylamino)-2-methylphenyl]-1-piperidinyl}propyl)propanamide 

Relevant academic research and scientific papers

Chemoenzymatic synthesis of pure enantiomeric 2-aryl propionic acids

A new chemoenzymatic procedure to obtain pure enantiomeric 2-arylpropionic acids is described. The one pot synthesis of (±)-2-arylpropionic acids is carried out by addition of dichlorocarbene to the C=O bond of arylmethylketones and hydrogenolysis of the additon product. The racemic mixture is resolved by enantiospecific hydrolysis of the racemic ethyl esters using native lipase from Candida rugosa. The good yields, the accessibility of the starting arylmethylketones and the stereospecificity of the enzymatic hydrolysis make the process interesting in order to obtain the same non steroidal antiinflammatory drugs such as Ibuprofen or Naproxen.

Enantioselective Synthesis of Chiral Carboxylic Acids from Alkynes and Formic Acid by Nickel-Catalyzed Cascade Reactions: Facile Synthesis of Profens

We report a stereoselective conversion of terminal alkynes to α-chiral carboxylic acids using a nickel-catalyzed domino hydrocarboxylation-transfer hydrogenation reaction. A simple nickel/BenzP* catalyst displayed high activity in both steps of regioselective hydrocarboxylation of alkynes and subsequent asymmetric transfer hydrogenation. The reaction was successfully applied in enantioselective preparation of three nonsteroidal anti-inflammatory profens (>90 % ees) and the chiral fragment of AZD2716.

Palladium-Catalyzed Asymmetric Markovnikov Hydroxycarbonylation and Hydroalkoxycarbonylation of Vinyl Arenes: Synthesis of 2-Arylpropanoic Acids

Asymmetric hydroxycarbonylation is one of the most fundamental yet challenging methods for the synthesis of carboxylic acids. Herein, we reported the development of a palladium-catalyzed highly enantioselective Markovnikov hydroxycarbonylation of vinyl arenes with CO and water. A monodentate phosphoramidite ligand L6 plays vital role in the reaction. The reaction tolerates a range of functional groups, and provides a facile and atom-economical approach to an array of 2-arylpropanoic acids including several commonly used non-steroidal anti-inflammatory drugs. The catalytic system has also enabled an asymmetric Markovnikov hydroalkoxycarbonylation of vinyl arenes with alcohols to afford 2-arylpropanates. Mechanistic investigations suggested that the hydropalladation is irreversible and is the regio- and enantiodetermining step, while hydrolysis/alcoholysis is probably the rate-limiting step.

Cobalt-Catalyzed Asymmetric Hydrogenation of α,β-Unsaturated Carboxylic Acids by Homolytic H2 Cleavage

The asymmetric hydrogenation of α,β-unsaturated carboxylic acids using readily prepared bis(phosphine) cobalt(0) 1,5-cyclooctadiene precatalysts is described. Di-, tri-, and tetra-substituted acrylic acid derivatives with various substitution patterns as well as dehydro-α-amino acid derivatives were hydrogenated with high yields and enantioselectivities, affording chiral carboxylic acids including Naproxen, (S)-Flurbiprofen, and a d-DOPA precursor. Turnover numbers of up to 200 were routinely obtained. Compatibility with common organic functional groups was observed with the reduced cobalt(0) precatalysts, and protic solvents such as methanol and isopropanol were identified as optimal. A series of bis(phosphine) cobalt(II) bis(pivalate) complexes, which bear structural similarity to state-of-the-art ruthenium(II) catalysts, were synthesized, characterized, and proved catalytically competent. X-band EPR experiments revealed bis(phosphine)cobalt(II) bis(carboxylate)s were generated in catalytic reactions and were identified as catalyst resting states. Isolation and characterization of a cobalt(II)-substrate complex from a stoichiometric reaction suggests that alkene insertion into the cobalt hydride occurred in the presence of free carboxylic acid, producing the same alkane enantiomer as that from the catalytic reaction. Deuterium labeling studies established homolytic H2 (or D2) activation by Co(0) and cis addition of H2 (or D2) across alkene double bonds, reminiscent of rhodium(I) catalysts but distinct from ruthenium(II) and nickel(II) carboxylates that operate by heterolytic H2 cleavage pathways.

Deracemizing α-Branched Carboxylic Acids by Catalytic Asymmetric Protonation of Bis-Silyl Ketene Acetals with Water or Methanol

We report a highly enantioselective catalytic protonation of bis-silyl ketene acetals. Our method delivers α-branched carboxylic acids, including nonsteroidal anti-inflammatory arylpropionic acids such as Ibuprofen, in high enantiomeric purity and high yields. The process can be incorporated in an overall deracemization of α-branched carboxylic acids, involving a double deprotonation and silylation followed by the catalytic asymmetric protonation.

Iron-catalysed enantioselective Suzuki-Miyaura coupling of racemic alkyl bromides

The first iron-catalysed enantioselective Suzuki-Miyaura coupling reaction has been developed. In the presence of catalytic amounts of FeCl2 and (R,R)-QuinoxP?, lithium arylborates are cross-coupled with tert-butyl α-bromopropionate in an enantioconvergent manner, enabling facile access to various optically active α-arylpropionic acids including several nonsteroidal anti-inflammatory drugs (NSAIDs) of commercial importance. (R,R)-QuinoxP? is specifically able to induce chirality when compared to analogous P-chiral ligands that give racemic products, highlighting the critical importance of transmetalation in the present asymmetric cross-coupling system.

MGLUR7 AGONIST COMPOUNDS FOR TREATING MGLUR7- REGULATED DISEASES, DISORDERS, OR CONDITIONS

The present invention provides compounds of formula (I) and pharmaceutically acceptable salts thereof wherein Z, R1, R2, R3, R4, R5 and R6 are as defined in the specification, a process for

Regio- and Stereoselective Oxidation of Styrene Derivatives to Arylalkanoic Acids via One-Pot Cascade Biotransformations

Green and selective oxidation methods are highly desired in chemical synthesis and manufacturing. In this work, we have developed a biocatalytic method for the regio- and stereoselective oxidation of styrene derivatives into arylacetic and (S)-2-arylpropionic acids via a one-pot epoxidation–isomerization–oxidation sequence. This was done via the engineering of Escherichia coli (StyABC-EcALDH) coexpressing styrene monooxygenase (SMO), styrene oxide isomerase (SOI) and aldehyde dehydrogenase (EcALDH) as an active and easily available whole-cell catalyst. Regioselective oxidation of styrene and 11 substituted styrenes using the E. coli cells was performed in a one-pot set-up, producing 12 phenylacetic acids in both high conversion and high yield. Engineering of E. coli (StyABC-ADH9v1) coexpressing SMO, SOI and ADH9v1 (a mutated alcohol dehydrogenase) led to biocatalysts capable of regio- and stereoselective oxidation of α-methylstyrene derivatives to the corresponding chiral acids. One-pot asymmetric synthesis of 4 (S)-2-arylpropionic acids was achieved in good conversion and excellent ee with the E. coli cells. This is a new type of asymmetric alkene oxidation to give chiral acids with no chemical counterpart thus far. The cascade bio-oxidation operates under mild conditions, uses molecular oxygen, exhibits very high regio- and enantioselectivity, and gives high conversion, thus providing a green and efficient method for the synthesis of arylacetic acids and (S)-2-arylpropionic acids directly from easily available styrenes. (Figure presented.).

Asymmetric Hydrogenation of α-Substituted Acrylic Acids Catalyzed by a Ruthenocenyl Phosphino-oxazoline-Ruthenium Complex

Asymmetric hydrogenation of various α-substituted acrylic acids was carried out using RuPHOX-Ru as a chiral catalyst under 5 bar H2, affording the corresponding chiral α-substituted propanic acids in up to 99% yield and 99.9% ee. The reaction could be performed on a gram-scale with a relatively low catalyst loading (up to 5000 S/C), and the resulting product (97%, 99.3% ee) can be used as a key intermediate to construct bioactive chiral molecules. The asymmetric protocol was successfully applied to an asymmetric synthesis of dihydroartemisinic acid, a key intermediate required for the industrial synthesis of the antimalarial drug artemisinin.

Ferrocenyl chiral bisphosphorus ligands for highly enantioselective asymmetric hydrogenation via noncovalent ion pair interaction

A new class of ferrocenyl chiral bisphosphorus ligand, Wudaphos, was developed, and exhibits excellent ee and activity (ee up to 99%, TON up to 20000) for the asymmetric hydrogenation of both 2-aryl and 2-alkyl acrylic acids through ion pair noncovalent interaction under base free and mild reaction conditions. Well-known anti-inflammatory drugs such as naproxen and ibuprofen together with the intermediate for the preparation of Roche ester and some bioactive compounds were also efficiently obtained with excellent ee. Control experiments were conducted and revealed that the ion pair noncovalent interaction and chain length played important roles.