42771-82-4

Usage

Uses

Used in Pharmaceutical Industry:
2-(2-fluoro-4-biphenylyl)-2-methylmalonic acid is used as an impurity in the production of Flurbiprofen, an anti-inflammatory drug. The presence of 2-(2-fluoro-4-biphenylyl)-2-methylmalonic acid in the drug is significant as it can affect the drug's efficacy, safety, and quality. It is essential to monitor and control the levels of this impurity during the manufacturing process to ensure the drug meets the required standards.
As an impurity in the pharmaceutical industry, 2-(2-fluoro-4-biphenylyl)-2-methylmalonic acid serves as a critical parameter in the quality control and assurance of Flurbiprofen. 2-(2-fluoro-4-biphenylyl)-2-methylmalonic acid's presence can impact the drug's performance, and thus, it is necessary to maintain its levels within acceptable limits to ensure the drug's effectiveness and safety for patients.

Upstream product

• 1020533-77-0 2-fluoro-4-(1,1-difluoroethyl)biphenyl 
• 124-38-9 carbon dioxide 
• 136434-77-0 4-bromo-3-fluoroiodobenzene 
• 42771-81-3 diethyl 2-(2-fluorobiphenyl-4-yl)-2-methylmalonate 
• 78543-08-5 2-(4-amino-3-fluorophenyl)-2-methylmalonic acid diethyl ester 
• 78543-06-3 diethyl 2-(3-fluoro-4-nitrophenyl)-2-methyl-malonate 
• 446-35-5 2,4-Difluoronitrobenzene 
• 70312-66-2 benzyl 2-(2-fluoro-biphenyl-4-yl)propionate 
• 113544-38-0 methyl 2-(2-fluoro-4-biphenylyl)propionate 
• 5104-49-4 fluorobiprofen 
• 543688-88-6 dimethyl 2-(2-fluoro-4-biphenylyl)-2-methylmalonate 

Downstream Products

• 5104-49-4 (S)-(+)-flurbiprofen 
• 5104-49-4 (R)-flurbiprofen 
• 5104-49-4 fluorobiprofen 

Relevant academic research and scientific papers

Enzymatic Synthesis of (R)-Flurbiprofen

α-Methyl-α-(2-fluoro-4-biphenylyl)propionic acid (flurbiprofen) was prepared from the corresponding malonic acid derivative via asymmetric decarboxylation catalyzed by an enzyme, arylmalonate decarboxylase (EC 4.1.1.76), in high chemical and optical yields.

Preparation of optically pure flurbiprofen via an integrated chemo-enzymatic synthesis pathway

In the synthesis of chiral molecules, the incorporation of enantioselective enzymatic conversions within the synthetic route often presents a useful approach. For the substitution of a chemical step with an enzymatic reaction, however, the complete synthetic route leading to and from this reaction needs to be considered carefully. An integrated approach, taking the possibilities and challenges of both types of conversions into account, can give access to chemo-enzymatic processes with great potential for effective synthesis strategies. We here report on the synthesis of enantiopure flurbiprofen using arylmalonate decarboxylase (AMDase, EC 4.1.1.76) in a chemo-enzymatic approach. Interestingly, practical considerations required shifting the enzymatic step to an earlier position in the synthetic route than previously anticipated. Engineered enzyme variants made it possible to obtain both (R)- and (S)-enantiomers of the target compound in excellent optical purity (>99%ee). The presented results underline that enzymes are most useful when they fit in a synthetic route, and that the optimization of biocatalytic steps and the planning of synthetic routes should be an integrated process.

Arylmalonate Decarboxylase-Catalyzed Asymmetric Synthesis of Both Enantiomers of Optically Pure Flurbiprofen

The bacterial decarboxylase (AMDase) catalyzes the enantioselective decarboxylation of prochiral arylmalonates with high enantioselectivity. Although this reaction would provide a highly sustainable synthesis of active pharmaceutical compounds such as flurbiprofen or naproxen, competing spontaneous decarboxylation has so far prevented the catalytic application of AMDase. Here, we report on reaction engineering and an alternate protection group strategy for the synthesis of these compounds that successfully suppresses the side reaction and provides pure arylmalonic acids for subsequent enzymatic conversion. Protein engineering increased the activity of the synthesis of the (S)-and (R)-enantiomers of flurbiprofen. These results demonstrated the importance of synergistic effects in the optimization of this decarboxylase. The asymmetric synthesis of both enantiomers in high optical purity (>99 %) and yield (>90 %) can be easily integrated into existing industrial syntheses of flurbiprofen, thus providing a sustainable method for the production of this important pharmaceutical ingredient. Optically pure flurbiprofen: A novel deprotection strategy for the preparation of the starting material combined with decarboxylase (AMDase) variants optimized by enzyme engineering allowed the asymmetric synthesis of both enantiomers of the non-steroidal anti-inflammatory drug (NSAID) flurbiprofen in excellent yield and optical purity.

Electrochemical carboxylation of α,α-difluorotoluene derivatives and its application to the synthesis of α-fluorinated nonsteroidal anti-inflammatory drugs

Electrochemical carboxylation of α,α-difluorotoluene derivatives resulted in an efficient fixation of carbon dioxide to give the corresponding α-fluorophenylacetic acids in good yields, and this reaction was successfully applied to the synthesis of α-fluorinated nonsteroidal anti-inflammatory drugs (NSAIDs). Georg Thieme Verlag Stuttgart.