65753-52-8

Usage

Uses

Used in Pharmaceutical Industry:
2-Fluoro-3-trifluoromethylpyridine is used as a synthetic intermediate for the development of antihypertensive β-adrenergic blocking agents. These agents are crucial in the treatment of high blood pressure and related cardiovascular conditions, as they help to regulate heart rate and blood vessel constriction.
Additionally, 2-Fluoro-3-trifluoromethylpyridine is utilized in the synthesis of HCV NS5B thumb pocket 2 allosteric inhibitors. These inhibitors play a vital role in the treatment of Hepatitis C, a viral infection that affects the liver and can lead to severe health complications if left untreated.

InChI:InChI=1/C6H3F3IN/c7-6(8,9)4-2-1-3-11-5(4)10/h1-3H

Upstream product

• 65753-47-1 2-chloro-3-trifluoromethyl-pyridine 
• 3796-23-4 3-(trifluoromethyl)pyridine 

Downstream Products

• 87394-63-6 1-(3-trifluoromethylpyridin-2-yl)piperazine 
• 183610-70-0 2-amino-3-trifluoromethylpyridine 
• 1276039-86-1 C₂₀H₁₃F₆N₃O₂ 
• 1276039-85-0 C₂₁H₁₄F₆N₂O₃ 
• 1276040-27-7 C₁₄H₉F₃INO₃ 
• 1276035-85-8 C₂₂H₁₅F₄N₃O₂ 
• 1276040-22-2 C₂₂H₁₈F₄N₂O₃ 
• 1163691-96-0 C₁₈H₁₉F₃N₂O₄ 
• 1115639-63-8 C₁₄H₁₀F₄N₂O₃ 

Relevant academic research and scientific papers

Tetramethylammonium Fluoride Alcohol Adducts for SNAr Fluorination

Nucleophilic aromatic fluorination (SNAr) is among the most common methods for the formation of C(sp2)-F bonds. Despite many recent advances, a long-standing limitation of these transformations is the requirement for rigorously dry, aprotic conditions to maintain the nucleophilicity of fluoride and suppress the generation of side products. This report addresses this challenge by leveraging tetramethylammonium fluoride alcohol adducts (Me4NF·ROH) as fluoride sources for SNAr fluorination. Through systematic tuning of the alcohol substituent (R), tetramethylammonium fluoride tert-amyl alcohol (Me4NF·t-AmylOH) was identified as an inexpensive, practical, and bench-stable reagent for SNAr fluorination under mild and convenient conditions (80 °C in DMSO, without the requirement for drying of reagents or solvent). A substrate scope of more than 50 (hetero) aryl halides and nitroarene electrophiles is demonstrated.

Preparation method of 2-hydroxyl-3-trifluoromethylpyridine

The invention relates to the technical field of chemical synthesis, and particularly discloses a preparation method of 2-hydroxyl-3-trifluoromethylpyridine. According to the preparation method disclosed by the invention, by using the 2-chloro-3-trifluoromethylpyridine as a starting raw material, fluorination is carried out under a certain condition so that 2-fluro-3-trifluoromethylpyridine is prepared; ammonolysis reaction is carried out on the 2-fluro-3-trifluoromethylpyridine so as to prepare 2-amino-3-trifluoromethylpyridine; then diazotization reaction is carried out to obtain the 2-hydroxyl-3-trifluoromethylpyridine. The preparation method disclosed by the invention is reliable in process, raw materials are sufficient and easy to get in the market, the production cost is low, an operation is simple, the yield is high, and scale production is facilitated; at present, a preparation method of the same or other components is never seen at home and abroad.

PROCESS FOR FLUORINATING COMPOUNDS

Disclosed are mild temperature (e.g., from 0 to 80°C) SNAr fluorinations of a variety of halide and sulfonate substituted aryl and heteroaryl substrates using NMe4F.

C-H FLUORINATION OF HETEROCYCLES WITH SILVER (II) FLUORIDE

The present invention provides compositions and methods for the selective C-H fluorination of nitrogen-containing heteroarenes with AgF2, which has previously been considered too reactive for practical, selective C-H fluorination. Fluorinated heteroarenes are prevalent in numerous pharmaceuticals, agrochemicals and materials. However, the reactions used to introduce fluorine into these molecules require pre-functionalized substrates or the use of F2 gas. The present invention provides a mild and general method for the C-H fluorination of nitrogen-containing heteroarene compounds to 2-fluoro-heteroarenes with commercially available AgF2. In various embodiments, these reactions occur at ambient temperature within one hour and occur with exclusive selectivity for fluorination at the 2-position. Exemplary reaction conditions are effective for fluorinating diazine heteroarenes to form a single fluorinated isomer.

Acyl azolium fluorides for room temperature nucleophilic aromatic fluorination of chloro- and nitroarenes

The reaction of acid fluorides with N-heterocyclic carbenes (NHCs) produces anhydrous acyl azolium fluorides. With appropriate selection of acid fluoride and NHC, these salts can be used for the room temperature SNAr fluorination of a variety of aryl chlorides and nitroarenes.

Anhydrous Tetramethylammonium Fluoride for Room-Temperature SNAr Fluorination

This paper describes the room-temperature SNAr fluorination of aryl halides and nitroarenes using anhydrous tetramethylammonium fluoride (NMe4F). This reagent effectively converts aryl-X (X = Cl, Br, I, NO2, OTf) to aryl-F under mild conditions (often room temperature). Substrates for this reaction include electron-deficient heteroaromatics (22 examples) and arenes (5 examples). The relative rates of the reactions vary with X as well as with the structure of the substrate. However, in general, substrates bearing X = NO2 or Br react fastest. In all cases examined, the yields of these reactions are comparable to or better than those obtained with CsF at elevated temperatures (i.e., more traditional halex fluorination conditions). The reactions also afford comparable yields on scales ranging from 100 mg to 10 g. A cost analysis is presented, which shows that fluorination with NMe4F is generally more cost-effective than fluorination with CsF.

Selective C-H fluorination of pyridines and diazines inspired by a classic amination reaction

Fluorinated heterocycles are prevalent in pharmaceuticals, agrochemicals, and materials. However, reactions that incorporate fluorine into heteroarenes are limited in scope and can be hazardous. We present a broadly applicable and safe method for the site-selective fluorination of a single carbon-hydrogen bond in pyridines and diazines using commercially available silver(II) fluoride. The reactions occur at ambient temperature within 1 hour with exclusive selectivity for fluorination adjacent to nitrogen. The mild conditions allow access to fluorinated derivatives of medicinally important compounds, as well as a range of 2-substituted pyridines prepared by subsequent nucleophilic displacement of fluoride. Mechanistic studies demonstrate that the pathway of a classic pyridine amination can be adapted for selective fluorination of a broad range of nitrogen heterocycles.

Halogen-Exchange Fluorination of Aromatic Halides with HF or HF-Base

Heteroatomic halides such as 2-chloropyrimidines and 2-chloropyridines, and 2,4-dinitrochlorobenzene underwent halogen-exchange fluorination with the treatment of HF or HF-base solutions to afford the corresponding fluorides in good yields.