924312-34-5

Usage

Chemical compound

4-(2-ethoxy-1,1-difluoro-2-oxoethyl)benzoic acid ethyl ester

Derivative

Ethyl ester of 4-(2-ethoxy-1,1-difluoro-2-oxoethyl)benzoic acid

Usage

Intermediate in the synthesis of pharmaceutical drugs, building block for organic compounds

Physical appearance

White to off-white solid

Solubility

Soluble in organic solvents such as ethanol and ether

Safety

Handle with caution, adhere to safety protocols to avoid health hazards

Upstream product

• 667-27-6 Ethyl bromodifluoroacetate 
• 128796-39-4 4-trifluoromethylphenylboronic acid 
• 4334-88-7 p-ethoxycarbonylphenylboronic acid 
• 383-62-0 ethyl 2-chloro-2,2-difluoroacetate 
• 5798-75-4 Ethyl 4-bromobenzoate 
• 98-88-4 benzoyl chloride 
• 93-89-0 benzoic acid ethyl ester 
• 51934-41-9 4-iodobenzoic acid ethyl ester 
• 205865-67-4 α-(trimethylsilyl)difluoroacetic acid ethyl ester 

Downstream Products

• 924312-35-6 ethyl 4-(1,1-difluoro-2-hydroxyethyl)benzoate 
• 64747-71-3 ethyl p-(difluoromethyl) benzoate 

Relevant academic research and scientific papers

Generation of Axially Chiral Fluoroallenes through a Copper-Catalyzed Enantioselective β-Fluoride Elimination

Herein we report the copper-catalyzed silylation of propargylic difluorides to generate axially chiral, tetrasubstituted monofluoroallenes in both good yields (27 examples >80%) and enantioselectivities (82-98% ee). Compared to previously reported synthetic routes to axially chiral allenes (ACAs) from prochiral substrates, a mechanistically distinct reaction has been developed: the enantiodiscrimination between enantiotopic fluorides to set an axial stereocenter. DFT calculations and vibrational circular dichroism (VCD) suggest that β-fluoride elimination from an alkenyl copper intermediate likely proceeds through a syn-β-fluoride elimination pathway rather than an anti-elimination pathway. The effects of the C1-symmetric Josiphos-derived ligand on reactivity and enantioselectivity were investigated. Not only does this report showcase that alkenyl copper species (like their alkyl counterparts) can undergo β-fluoride elimination, but this elimination can be achieved in an enantioselective fashion.

Palladium-Catalyzed Para-Selective Difluoromethylation of Arene Esters

Highly efficient, palladium-catalyzed, para-selective difluoromethylation of arene esters has been developed using [1,1′-biphenyl]-2-dicyclohexylphosphine as the effective ligand. A wide variety of arene esters bearing various functional groups were all compatible with the reaction conditions, leading to para-difluoromethylated products in moderate to good yields. Moreover, benzoylamide and benzenesulfonamide were also well-tolerated, suggesting that this novel catalyst system has broad applications to a variety of substrates.

Lewis acid-mediated defluorinative [3+2] cycloaddition/aromatization cascade of 2,2-difluoroethanol systems with nitriles

The properties of C?F bonds, including high thermal and chemical stability, make derivatization of organic fluorine-containing compounds by the activation of the C?F bond and subsequent functionalization quite challenging. We herein report a Lewis acid-mediated defluorinative cycloaddition/aromatization cascade of 2,2-difluoroethanols with nitriles as a novel synthetic method for the preparation of 2,4,5-trisubstituted oxazoles. This reaction, which involves cleavage of two C?F bonds and the consecutive formation of C?O and C?N bonds in a one-pot fashion, features a broad substrate scope and moderate to high reaction yields. Mechanistic studies revealed that the reaction is initiated by the Lewis acid-mediated ring closure of the 2,2-difluoroethanol to produce the fluoroepoxide intermediate. (Figure presented.).

Palladium-Catalyzed Cross-Coupling of Ethyl Bromodifluoroacetate with Aryl Bromides or Triflates and Cross-Coupling of Ethyl Bromofluoroacetate with Aryl Iodides

A palladium-catalyzed Negishi cross-coupling reaction of ethyl bromodifluoroacetate with aryl bromides or aryl triflates to construct C(sp2)-CF2 bonds is described. The reaction was conducted under mild reaction conditions, and no preparation of organozinc reagents is required. This is the first report encompassing the conversion of aryl triflates into products containing C-CF2 bonds. In addition, the construction of C(sp2)-CHF bonds was achieved under mild conditions via a cross-coupling of aryl iodides with ethyl bromofluoroacetate.

Method of manufacturing arom. defluoromethyl compd.

PROBLEM TO BE SOLVED: To provide a method for easily producing an aromatic compound having a difluoromethyl group in high yield while using a reagent having low toxicity. SOLUTION: The method for producing the aromatic difluoromethyl compound includes reacting an aromatic difluoroacetic acid in the presence of a metal halide (especially potassium fluoride). COPYRIGHT: (C)2011,JPOandINPIT

Nickel-catalyzed cross-coupling of functionalized difluoromethyl bromides and chlorides with aryl boronic acids: A general method for difluoroalkylated arenes

Transition-metal-catalyzed difluoroalkylation of aromatics remains challenging despite the importance of difluoroalkylated arenes in medicinal chemistry. Herein, the first successful example of nickel-catalyzed difluoroalkylation of aryl boronic acids is described. The reaction allows access to a variety of functionalized difluoromethyl bromides and chlorides, and paves the way to highly cost-efficient synthesis of a wide range of difluoroalkylated arenes. The notable features of this protocol are its high generality, excellent functional-group compatibility, low-cost nickel-catalyst, and practicality for gram-scale production, thus providing a facile method for applications in drug discovery and development.

Palladium-catalyzed difluoroalkylation of aryl boronic acids: A new method for the synthesis of aryldifluoromethylated phosphonates and carboxylic acid derivatives

The palladium-catalyzed difluoroalkylation of aryl boronic acids with bromodifluoromethylphosphonate, bromodifluoroacetate, and further derivatives has been developed. This method provides a facile and useful access to a series of functionalized difluoromethylated arenes (ArCF2PO(OEt) 2, ArCF2CO2Et, and ArCF2CONR 1R2) that have important applications in drug discovery and development. Preliminary mechanistic studies reveal that a single electron transfer (SET) pathway may be involved in the catalytic cycle. Palladium does it: The palladium-catalyzed difluoroalkylation of aryl boronic acids with bromodifluoromethylphosphonate, bromodifluoroacetate, and further derivatives has been developed (see scheme). Preliminary mechanistic studies reveal that a single electron transfer (SET) pathway may be involved in the catalytic cycle. Copyright

METHOD FOR PRODUCING AROMATIC DIFLUOROACETIC ACID ESTER

Disclosed is a method for producing a compound having a difluoromethylene group at an even lower cost and with excellent yield. The production method of the present invention is a method for producing an aromatic difluoroacetic acid ester, which comprises reacting an iodobenzene containing an electro attracting group and an α-silyl difluoroacetic acid ester in the presence of a metal halide.

A new method for aromatic difluoromethylation: Copper-catalyzed cross-coupling and decarboxylation sequence from aryl iodides

A new methodology for aromatic difluoromethylation is described. Aryl iodides reacted with α-silyldifluoroacetates upon treatment with copper catalyst in DMSO or DME to give the corresponding aryldifluoroacetates in moderate to good yields. The subsequent hydrolysis of aryldifluoroacetates and KF-promoted decarboxylation afforded a variety of difluoromethyl aromatics.

PYRIDONE COMPOUND

An active ingredient is a compound represented by the general formula [I]: [wherein R1 and R2 represent a lower alkyl group, a C3-6 cycloalkyl group or the like, X1 and X2 represent methine, an Ar-Ys