Method for synthesizing alpha, alpha-difluoroketone compound

A compound and difluoroketone technology, which is applied in the field of organic synthesis, can solve the problems of difficulty in obtaining α,α-difluoroester and high price, and achieve the effects of high reaction efficiency, mild reaction conditions, and cheap and easy-to-obtain raw materials

Active Publication Date: 2021-03-16
TAIZHOU UNIV
View PDF2 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In 2015, Altman's research group reported the first palladium-catalyzed decarboxylation and alkylation reaction to generate α,α-difluoroketones in situ. The substrate of this reaction has a wide range of applications, but the substrate α,α-difluoroester It is not easy to obtain, and it needs to be prepa

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Method for synthesizing alpha, alpha-difluoroketone compound
  • Method for synthesizing alpha, alpha-difluoroketone compound
  • Method for synthesizing alpha, alpha-difluoroketone compound

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1~19

[0029] Add alcohol 1 (1.0mmol), difluoroenol silyl ether 2 (1.05mmol, 1.05equiv), solvent (3.0mL), catalyst (0.1mmol, 10.5μL) to the Shrek tube successively, react at room temperature, TLC point The plate monitors the reaction, and the reaction is completed in about 2-12 hours. After the reaction was over, the solvent was removed under reduced pressure, and the concentrate was separated and purified by column chromatography to obtain product 3. The reaction conditions and reaction results were as follows:

[0030]

Embodiment 20~61

[0032] Alcohol (1.0mmol), difluoroenol silyl ether 2 (1.05mmol, 1.05equiv), dichloromethane (3.0mL), HFIP (0.1mmol, 10.5μL) were sequentially added to the Shrek tube, reacted at room temperature, TLC Spot the plate to monitor the reaction, and monitor the completion of the reaction. After the reaction was finished, the solvent was removed under reduced pressure, and the concentrate was separated and purified by column chromatography to obtain the product. The results are as follows:

[0033]

[0034] The characterization data of part products in the embodiment are as follows:

[0035]

[0036] 2,2-difluoro-3-(4-methoxyphenyl)-1-phenylpropan-1-one (4): The crude product was purified by column chromatography, and the eluent was petroleum ether / ethyl acetate (50 / 1, v / v) Compound 4 was obtained (white solid, 114.6 mg, 83% yield). M.p.: 146–147°C; 1 H NMR (400MHz, CDCl 3 ) δ8.04(d, J=7.5Hz, 2H), 7.65–7.54(m, 1H), 7.51–7.41(m, 2H), 7.22(d, J=8.6Hz, 2H), 6.88–6.81(m ,2H),3...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

Abstract

The invention discloses a method for synthesizing an alpha, alpha-difluoroketone compound, which comprises the following steps: reacting an alcohol compound with a difluoroenol silyl ether compound inan organic solvent under the action of a catalyst (fluoro alcohol, Lewis acid and acid), and carrying out after-treatment after the reaction is finished to obtain the alpha, alpha-difluoroketone compound. Reaction conditions are mild, reaction efficiency is high, raw materials are cheap and easy to obtain, and important application significance is achieved.

Description

technical field [0001] The invention belongs to the field of organic synthesis, and in particular relates to a method for synthesizing α,α-difluoroketone compounds. Background technique [0002] α,α-Difluoroketones are widely used in medicinal chemistry because of their unique physicochemical properties and biological activities. Such compounds are often used as enzyme inhibitors (Formula 1). At the same time, α,α-difluoroketones are important building blocks for the synthesis of various fluorine-containing complex compounds. Due to the strong inductive effect of the two fluorine atoms, α,α-difluoroenols cannot directly interact with electrophiles (C(sp 3 )) reaction to obtain α,α-difluoroketones. Therefore, the direct nucleophilic substitution reaction of fluorine-containing enols with electrophiles is somewhat challenging. [0003] [0004] Currently, the synthesis of α,α-difluoroketones mainly relies on electrophilic fluorinating reagents, prefunctionalized deoxyfl...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
IPC IPC(8): C07C45/00C07C49/84C07C49/83C07C49/813C07C67/343C07C69/76C07C69/712C07F17/02C07D317/54C07D311/82C07D333/56C07H15/203C07H1/00
CPCC07C45/00C07C67/343C07F17/02C07D317/54C07D311/82C07D333/56C07H15/203C07H1/00C07C2601/02C07C2602/08C07C2603/18C07C2603/34C07C2601/16C07C2601/10C07C2602/10C07C49/84C07C49/83C07C49/813C07C69/76C07C69/712
Inventor 李金山王治明吴海建奚文学
Owner TAIZHOU UNIV
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products