1493-03-4Relevant articles and documents
The Preparation and Allylation of Difluoromethylcadmium
Hartgraves, Greg A.,Burton, Donald J.
, p. 425 - 430 (1988)
The reaction of iodo- and bromodifluoromethane with cadmium powder in DMF at room temperature provides a useful route to difluoromethylcadmium.This partially fluorinated cadmium reagent exhibits excellent thermal stability to temperatures of 65-75 degC, and rapid decomposition does not occur until 105 degC.This reagent reacts readily with allylic halides and shows promise as a new difluoromethylation reagent.
Continuous Process for Preparing the Difluoromethylating Reagent [(DMPU)2Zn(CF2H)2] and Improved Synthesis of the ICHF2Precursor
Monfette, Sebastien,Fang, Yuan-Qing,Bio, Matthew M.,Brown, Adam R.,Crouch, Ian T.,Desrosiers, Jean-Nicolas,Duan, Shengquan,Hawkins, Joel M.,Hayward, Cheryl M.,Peperni, Nikita,Rainville, Joseph P.
, p. 1077 - 1083 (2020)
Complex [(DMPU)2Zn(CF2H)2] 1 is a crystalline organometallic reagent with utility in various catalytic difluoromethylation reactions under mild conditions. Unfortunately, this reagent is not commercially available and the procedure for the preparation of this air- and moisture-sensitive zinc complex has only been reported on a small scale. Herein, we report the development of a continuous process for the preparation of reagent 1 on >100 g scale by using a continuous stirred-tank reactor. The key to success is the design of a continuous reactive crystallization process in which the precipitation of the zinc complex 1 is driven by its low solubility in the reaction solvent. The improved synthesis of the iododifluoromethane precursor 2 from readily available bromodifluoroacetic acid further enables the synthesis of complex 1 on a larger scale.
THE HYDROLYSIS OF BROMODIFLUOROMETHYLTRIPHENYLPHOSPHONIUM BROMIDE
Flynn, R. M.,Manning, R. G.,Kessler, R. M.,Burton, D. J.,Hansen, S. W.
, p. 525 - 532 (1981)
Hydrolysis of +Br- afforded a high yield of bromodifluoromethane and triphenylphosphine oxide.Hydrolysis in the presence of a radioactive isotope of bromine or sodium iodide gave unequivocal evidence that the mechanism for this reaction proceeds through a difluorocarbene intermediate.
DIFLUOROMETHYL IODO COMPOUNDS AND METHODS
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Paragraph 0033-0039, (2021/08/27)
The present application is related to an improved process for synthesising 1 -(difluoromethyl)-3-iodobicyclo[1.1.1 ]pentane from difluoromethyl iodide and [1.1.1]propellane. Difluoromethyl iodide is made by reacting an iodide salt with chlorodifluoroacetic acid in the presence of a solvent such as sulfolane and an inorganic base, [1.1.1]propellane is synthesised by reacting 1,1-dibromo- 2,2-cis(chloromethyl)cyclopropane with a reagent such as magnesium, methyllithium or phenyllithium.
NANOPARTICLE FORMULATION OF BCL-2 INHIBITOR
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Paragraph 0245, (2021/01/29)
Various albumin nanoparticle Bcl-2 inhibitor formulations are described, along with methods of using them to treat conditions characterized by excessive cellular proliferation, such as cancer and tumors. In various embodiments, such Bcl-2 inhibitor formulations contain albumin and a compound of the following Formula (I), or a pharmaceutically acceptable salt thereof, where the variables in Formula (I) are defined herein.
BCL-2 PROTEIN INHIBITORS
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Paragraph 0154, (2021/01/29)
Various Bcl-2 protein inhibitors are described, along with methods of using them to treat conditions characterized by excessive cellular proliferation, such as cancer and tumors. In various embodiments the Bcl-2 protein inhibitors are compounds or pharmaceutically acceptable salts of the following Formula (I), where the variables in Formula (I) are defined herein.
Production method of fluoroalkyl iodide
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Paragraph 0118-0120, (2020/02/18)
The invention discloses a production method of a fluoroalkyl iodide, and particularly discloses a production method of a fluoroalkyl iodide as shown in a formula (I) as shown in the specification. Theproduction method of the fluoroalkyl iodide as shown in the formula (I) as shown in the specification comprises the following step: in a first solvent, subjecting a compound as shown in a formula (II) as shown in the specification and an iodide to an iodination reaction as shown in the specification. The raw materials used in the method are easy to obtain, and prices are low; and the method is high in conversion rate and yield, and the tolerability to functional groups is high.
Ligand-Less Iron-Catalyzed Aromatic Cross-Coupling Difluoromethylation of Grignard Reagents with Difluoroiodomethane
Motohashi, Hirotaka,Kato, Miki,Mikami, Koichi
, p. 6483 - 6490 (2019/05/16)
Iron-catalyzed cross-coupling difluoromethylations of the Grignard reagents with difluoroiodomethane provide various aromatic difluoromethyl products in good yields, not employing sterically demanding ligands. Difluoromethylations proceed within 30 min at -20 °C with 2.0 equiv of the Grignard reagents and FeCl3 or Fe(acac)3 (2.5 mol %). Mechanistic investigations clarify difluoromethyl radical intervention; Fe(0) ate is initially generated. Single-electron transfer from Fe(0) ate to difluoroiodomethane takes place. Recombination with aryl groups gives Ar-CF2Hs. The catalyst can be regenerated by the Grignard reagents.
BENZAMIDE COMPOUNDS
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Paragraph 0337, (2019/07/30)
Compounds of Formula (I) are provided herein. Such compounds, as well as pharmaceutically acceptable salts and compositions thereof, are useful for treating diseases or conditions, including conditions characterized by excessive cellular proliferation, such as cancer and tumors, as well as viral infections such as HIV.
Nickel-Catalyzed Aromatic Cross-Coupling Difluoromethylation of Grignard Reagents with Difluoroiodomethane
Motohashi, Hirotaka,Mikami, Koichi
supporting information, p. 5340 - 5343 (2018/09/12)
The nickel-catalyzed cross-coupling difluoromethylation of the Grignard reagents with difluoroiodomethane is shown to provide the corresponding aromatic difluoromethyl products in excellent to moderate yields. The difluoromethylation proceeds smoothly within 1 h at room temperature with 1.5 equiv of the Grignard reagents in the presence of Ni(cod)2/TMEDA (2.5-0.5 mol %). Mechanistic studies clarify that the oxidative addition of the Ni(0) catalyst to difluoroiodomethane provides the TMEDA-Ni(II)(CF2H)I complex. This intermediate is transformed to TMEDA-Ni(II)(CF2H)Ph via transmetalation with PhMgBr. The reductive elimination takes place to give the aromatic cross-coupling difluoromethylation product along with regeneration of the TMEDA-Ni(0) catalyst. Electron paramagnetic resonance (EPR) and radical clock analyses of the nickel-catalyzed reaction provide no EPR active Ni(I) and Ni(III) species at around g = 2 and only a trace amount of the cyclization product.
