16184-89-7

Usage

Uses

Used in Pharmaceutical Industry:
4'-BROMO-2,2,2-TRIFLUOROACETOPHENONE is used as a key intermediate in the synthesis of carbonyl-bridged bithiazole derivatives, which are important compounds in the development of pharmaceuticals targeting various medical conditions.
Used in Obesity Treatment:
4'-BROMO-2,2,2-TRIFLUOROACETOPHENONE is used as a reagent for synthesizing MK-5046, a selective Bombesin receptor subtype-3 agonist. 4'-BROMO-2,2,2-TRIFLUOROACETOPHENONE is utilized in the treatment of obesity, helping to regulate appetite and promote weight loss.
Used in Chemical Synthesis:
4'-BROMO-2,2,2-TRIFLUOROACETOPHENONE, due to its unique chemical structure, is also employed in various chemical synthesis processes, particularly in the creation of novel compounds with potential applications in different industries, such as materials science and agrochemicals.

InChI:InChI=1/C10H9F3O/c1-2-9(14)7-5-3-4-6-8(7)10(11,12)13/h3-6H,2H2,1H3

Upstream product

• 383-63-1 ethyl trifluoroacetate, 
• 22480-64-4 4-bromophenyllithium 
• 18620-02-5 (4-bromophenyl)magnesium bromide 
• 407-25-0 trifluoroacetic anhydride 
• 16261-79-3 O₂NCF₂C(4-Br-C₆H₄)(OH)CF₃ 
• 106-37-6 1.4-dibromobenzene 
• 108-86-1 bromobenzene 
• 431-47-0 trifluoroacetic acid-methyl ester 
• 80418-12-8 1-(4-bromo-phenyl)-2,2,2-trifluoro-ethanol 
• 583-53-9 2,3-dibromobenzene 
• 81290-20-2 (trifluoromethyl)trimethylsilane 
• 586-75-4 4-chlorobenzoyl chloride 
• 104863-67-4 N-methoxy-N-methyltrifluoroacetamide 
• 1122-91-4 4-bromo-benzaldehyde 

Downstream Products

• 80418-12-8 1-(4-bromo-phenyl)-2,2,2-trifluoro-ethanol 
• 80418-12-8 (R)-1-(4-bromophenyl)-2,2,2-trifluoroethanol 
• 76911-73-4 (S)-1-(4-bromophenyl)-2,2,2-trifluoroethan-1-ol 
• 70783-32-3 2,2,2-trifluoro-1-(4-phenoxyphenyl)-ethanone 
• 413598-07-9 ((1-(4-bromophenyl)-2,2-difluorovinyl)oxy)trimethylsilane 
• 935265-36-4 1-(4-(2-(1-(tert-butyldimethylsilyloxy)-7-phenylheptyl)oxazol-5-yl)phenyl)-2,2,2-trifluoroethanone 
• 945428-26-2 1-(1-(4-bromophenyl)-2,2,2-trifluoroethylidene)hydrazine 
• 292145-64-3 1-(4-bromophenyl)-2,2,2-trifluoroethanone oxime 
• 122243-32-7 4-(1,1,1-trifluoro-2-hydroxypropan-2-yl)benzonitrile 
• 122242-95-9 Toluene-4-sulfonic acid 1-(4-bromo-phenyl)-2,2,2-trifluoro-1-methyl-ethyl ester 
• 128626-62-0 3-Nitro-benzenesulfonic acid 1-(4-cyano-phenyl)-2,2,2-trifluoro-1-methyl-ethyl ester 
• 179894-88-3 1,2-Dihydro-2,2,4-trimethyl-6-[4-(trifluoroacetyl)phenyl]quinoline 
• 916347-65-4 (2R,4R)-2-(4-bromophenyl)-4-[(methylthio)methyl]-2-(trifluoromethyl)-1,3-oxazolidine 
• 916347-79-0 (2S,4R)-2-(4-bromophenyl)-4-[(methylthio)methyl]-2-(trifluoromethyl)-1,3-oxazolidine 

Relevant academic research and scientific papers

Enantioselective Synthesis of Trifluoromethyl α,β-Unsaturated δ-Lactones via Vinylogous Aldol-Lactonization Cascade

The novel vinylogous aldol-lactonization cascade of alkylidene oxindole with trifluoromethyl ketones is presented. The reaction, catalyzed by a bifunctional tertiary amine, provides an efficient application of the vinylogous reactivity of alkylidene oxindoles for the preparation of enantioenriched trifluoromethylated α,β-unsaturated δ-lactones.

Palladium-catalyzed carbonylative coupling of aryl iodides with an organocopper reagent: A straightforward procedure for the synthesis of aryl trifluoromethyl ketones

A palladium-catalyzed carbonylative coupling of aryl iodides with a (trifluoromethyl)copper reagent has been developed. A wide range of substrates have been transformed into their corresponding trifluoromethyl ketones in good to excellent yields under mild conditions with high efficiency and excellent functional-group compatibility. Preliminary mechanistic investigations suggest that the transmetallation of an acylpalladium intermediate with the (trifluoromethyl)copper reagent seems to be involved in the catalytic cycle. Notably, this report represents one of the few studies on carbonylative coupling with organocopper reagents.

Direct Synthesis of Tri-/Difluoromethyl Ketones from Carboxylic Acids by Cross-Coupling with Acyloxyphosphonium Ions

A simple and straightforward approach to the synthesis of trifluoromethyl and difluoromethyl ketones from widely available carboxylic acids is disclosed. The transformation utilizes an acyloxyphosphonium ion as the active electrophile, conveniently generated in situ from the carboxylic acid substrate by using commodity chemicals. The utility of the reaction system is exemplified by its chemoselectivity, with tolerance to a variety of important functional groups. The late-stage functionalization of carboxylic acid active pharmaceutical ingredients and pharmaceutically relevant compounds is also discussed.

Synthesis of trifluoromethyl ketones by nucleophilic trifluoromethylation of esters under a fluoroform/KHMDS/triglyme system

A straightforward method that enables the formation of biologically attractive trifluoromethyl ketones from readily available methyl esters using the potent greenhouse gas fluoroform (HCF3, HFC-23) was developed. The combination of fluoroform and KHMDS in triglyme at ?40 °C was effective for this transformation, with good yields as high as 92%. Substrate scope of the trifluoromethylation procedure was explored for aromatic, aliphatic, and conjugated methyl esters. This study presents a straightforward trifluoromethylation process of various methyl esters that convert well to the corresponding trifluoromethyl ketones. The tolerance of various pharmacophores under the reaction conditions was also explored.

Highly enantioselective construction of CF3-bearing all-carbon quaternary stereocenters: Hiral spiro-fused bisoxazoline ligands with 1,1′-binaphthyl sidearm for asymmetric Michael-type Friedel-Crafts reaction

A novel class of chiral spiro-fused bisoxazoline ligands possessing a deep chiral pocket was prepared. The developed ligands have been employed in the nickel-catalyzed highly enantioselective Michael-type Friedel-Crafts reaction, affording the products bearing a trifluoromethylated all-carbon quaternary stereocenter with moderate to excellent yields (up to 99%) and good to excellent enantioselectivies (up to > 99.9% ee). Moreover, a proposed model of chiral pocket revealed that the attack of indole from the Re-face of β-CF3-β-disubstituted nitroalkene was favorable.

Photochemical C-H Activation Enables Nickel-Catalyzed Olefin Dicarbofunctionalization

Alkenes, ethers, and alcohols account for a significant percentage of bulk reagents available to the chemistry community. The petrochemical, pharmaceutical, and agrochemical industries each consume gigagrams of these materials as fuels and solvents each year. However, the utilization of such materials as building blocks for the construction of complex small molecules is limited by the necessity of prefunctionalization to achieve chemoselective reactivity. Herein, we report the implementation of efficient, sustainable, diaryl ketone hydrogen-atom transfer (HAT) catalysis to activate native C-H bonds for multicomponent dicarbofunctionalization of alkenes. The ability to forge new carbon-carbon bonds between reagents typically viewed as commodity solvents provides a new, more atom-economic outlook for organic synthesis. Through detailed experimental and computational investigation, the critical effect of hydrogen bonding on the reactivity of this transformation was uncovered.

One-Pot Successive Turbo Grignard Reactions for the Facile Synthesis of α-Aryl-α-Trifluoromethyl Alcohols

A novel straightforward one-pot methodology for two successive turbo Grignard reagent (iPrMgCl·LiCl) reactions, was developed for a facile synthesis of α-aryl-α-trifluoromethyl alcohols, motifs of value in pharmaceutical chemistry. The method displayed broad functional group tolerance, including reducible groups. Dual roles of iPrMgCl·LiCl were exploited in the tandem reaction with commercially available iodoarenes or iodoheteroarenes and 2,2,2-trifluoroethyl trifluoroacetate. The process encompasses three successive reactions in a one-pot process: the iPrMgCl·LiCl-mediated iodine/magnesium-exchange reaction of iodoarenes or iodoheteroarenes; nucleophilic addition of various generated aryl or heteroarylmagnesium reagents to 2,2,2-trifluoroethyl trifluoroacetate; and the reduction of in-situ generated aryl trifluoromethyl ketones with iPrMgCl·LiCl, to produce the corresponding α-aryl or α-heteroaryl-α-trifluoromethyl alcohols bearing various substituents, including reducible functional groups in good to excellent yields.

Palladium-catalyzed fluoroacylation of (Hetero)arylboronic acid with fluorothioacetates at ambient temperature

A palladium-catalyzed fluoroacylation of (hetero)aryl boronic acid with the fluorothioacetates is described at ambient temperature. A variety of aryl, and heteroaryl boronic acids are compatible in the reaction, affording the corresponding fluoroalkyl ketones in moderate to good yields. Further late-stage di-, and trifluoroacylation of drug molecule clofibrate and estrone demonstrated the synthetic practicability of this protocol.2009 Elsevier Ltd. All rights reserved.

A Hammett Study of Clostridium acetobutylicum Alcohol Dehydrogenase (CaADH): An Enzyme with Remarkable Substrate Promiscuity and Utility for Organic Synthesis

Described is a physical organic study of the reduction of three sets of carbonyl compounds by the NADPH-dependent enzyme Clostridium acetobutylicum alcohol dehydrogenase (CaADH). Previous studies in our group have shown this enzyme to display broad substrate promiscuity, yet remarkable stereochemical fidelity, in the reduction of carbonyl compounds, including α-, β- and γ-keto esters (d -stereochemistry), as well as α,α-difluorinated-β-keto phosphonate esters (l -stereochemistry). To better mechanistically characterize this promising dehydrogenase enzyme, we report here the results of a Hammett linear free-energy relationship (LFER) study across three distinct classes of carbonyl substrates; namely aryl aldehydes, aryl β-keto esters and aryl trifluoromethyl ketones. Rates are measured by monitoring the decrease in NADPH fluorescence at 460 nm with time across a range of substrate concentrations for each member of each carbonyl compound class. The resulting v 0 versus [S] data are subjected to least-squares hyperbolic fitting to the Michaelis-Menton equation. Hammett plots of log(V max) versus σ X yield the following Hammett parameters: (i) for p -substituted aldehydes, ρ = 0.99 ± 0.10, ρ = 0.40 ± 0.09; two domains observed, (ii) for p -substituted β-keto esters ρ = 1.02 ± 0.31, and (iii) for p -substituted aryl trifluoromethyl ketones ρ = -0.97 ± 0.12. The positive sign of ρ indicated for the first two compound classes suggests that the hydride transfer from the nicotinamide cofactor is at least partially rate-limiting, whereas the negative sign of ρ for the aryl trifluoromethyl ketone class suggests that dehydration of the ketone hydrate may be rate-limiting for this compound class. Consistent with this notion, examination of the 13 C NMR spectra for the set of p -substituted aryl trifluo romethyl ketones in 2percent aqueous DMSO reveals significant formation of the hydrate (gem -diol) for this compound family, with compounds bearing the more electron-withdrawing groups showing greater degrees of hydration. This work also presents the first examples of the CaADH-mediated reduction of aryl trifluoromethyl ketones, and chiral HPLC analysis indicates that the parent compound α,α,α-trifluoroacetophenone is enzymatically reduced in 99percent ee and 95percent yield, providing the (S)-stereoisomer, suggesting yet another compound class for which this enzyme displays high enantioselectivity.

CONDENSED IMIDAZOLE DERIVATIVES SUBSTITUTED BY TERTIARY HYDROXY GROUPS AS PI3K-GAMMA INHIBITORS

This application relates to compounds of Formula (I): or pharmaceutically acceptable salts thereof, which are inhibitors of PI3K-y which are useful for the treatment of disorders such as autoimmune diseases, cancer, cardiovascular diseases, and neurodegenerative diseases.