156570-10-4

Usage

Type of compound

Substituted benzene compound

Structure

One chlorine atom attached to a carbon atom and two fluorine atoms attached to different carbon atoms of the benzene ring

Usage

Organic synthesis, chemical research, potential applications in pharmaceuticals, agrochemicals, and specialty chemicals

Safety

Handle with caution and follow safety protocols due to potential hazardous properties

Further research

Additional research and testing may be needed to fully understand the potential uses and risks associated with this chemical

Upstream product

• 51336-94-8 2-chloro-1-(2,4-dichlorophenyl)ethanone 
• 13170-43-9 (trimethylsilyl)methylmagnesium chloride 
• 2344-80-1 Chloromethyltrimethylsilane 
• 141113-36-2 2-(2,4-difluorophenyl)allyl alcohol 

Downstream Products

• 159276-62-7 diethyl 2-[2-(2,4-difluorophenyl)-2-propen-1-yl]-1,3-propanedioate 
• 171228-49-2 posaconazote 
• 165115-73-1 2-[2-(2,4-difluorophenyl)-2-propene-1-yl]-1, 3-propanediol 
• 192448-07-0 2-methylpropanoic acid [(2S)-4-(2,4-difluorophenyl)-2-hydroxymethyl-4-penten-1-yl] ester 
• 1350560-52-9 C₁₆H₁₉F₂IO₃ 
• 149809-43-8 (2R-cis)-2-(2,4-difluorophenyl)-4-[[(4-methylphenyl)sulfonyloxy]methyl]-2-[(1H-1,2,4-triazol-1-yl)methyl]tetrahydrofuran 
• 184378-04-9 C₃₀H₃₂F₂N₆O₂ 
• 1350560-57-4 C₃₇H₄₄F₂N₈O₅ 
• 160709-02-4 ((3R,5R)-5-((1H-1,2,4-triazole-1-yl) methyl)-5-(2,4-difluorophenyl) tetrahydrofuran-3-yl)methanol 
• 1350466-82-8 C₁₄H₁₅F₂N₃O₂*ClH 
• 1350560-54-1 C₁₄H₁₅F₂N₃O₂*ClH 

Relevant academic research and scientific papers

Synthesis method of diethyl 2-[2-(2,4-difluorophenyl)allyl]-1,3-malonate

The invention relates to a synthesis method of diethyl 2-[2-(2,4-difluorophenyl)allyl]-1,3-malonate. The synthesis method comprises the following steps: mixing 3-chloro-1,2-propanediol and 1,3-difluorobenzene, and adding a catalyst to react; adding the mixture into a hydrochloric acid solution at 5 to -5 DEG C, stirring uniformly, extracting 3-5 times by using dichloromethane as an extractant, and washing the extracting solution with a saturated NaHCO3 solution, water and a saturated saline solution; drying with anhydrous Na2SO4, filtering, evaporating the dichloromethane to obtain 1-chloro-2-(2,4-difluorophenyl)-3-propanol, mixing the 1-chloro-2-(2,4-difluorophenyl)-3-propanol and potassium hydrogen sulfate into chlorobenzene, and heating under reflux for 10-16 hours; and washing with water to a neutral state, drying with anhydrous Na2SO4, filtering, distilling to obtain 1-(1-chloromethylvinyl)-2,4-difluorobenzene, dissolving in DMSO (dimethyl sulfoxide), adding diethyl malonate and hydroxide to react, extracting, washing and carrying out reduced pressure distillation to obtain the target product. The synthesis route is disclosed in the specification.

Synthesis method of 2-[2-(2,4-diflurophenyl)-2-propen-1-yl)-1,3-propanediol

The invention relates to a synthesis method of 2-[2-(2,4-diflurophenyl)-2-propen-1-yl)-1,3-propanediol. The synthesis method comprises the following steps: mixing 2-chloromethyl epoxy propane with 1,3-difluorobenzene to perform reaction under an effect of catalyst to obtain 2-(2,4-diflurophenyl)-1-chloro-3-propanol; mixing 2-(2,4-diflurophenyl)-1-chloro-3-propanol with potassium hydrogen sulfate and chlorobenzene to perform reaction to obtain 1-(1-chloromethylvinyl)-2,4-difluorobenzene; enabling 1-(1-chloromethylvinyl)-2,4-difluorobenzene to react with diethyl malonate to obtain a product 2-[2-(2,4-diflurophenyl)propenyl]-1,3-diethyl malonate; dissolving 2-[2-(2,4-diflurophenyl)-2-propen-1-yl]-1,3-diethyl malonate in mixed solvent formed by isopropanol and water to react with borohydride to obtain a target product 2-[2-(2,4-diflurophenyl)-2-propen-1-yl)-1,3-propanediol; a synthesis route is as shown in the accompanying drawing.

Synthesis method of 2-[2-(2,4-diflurophenyl)-2-propylene-1-yl]-1,3-propylene glycol

The invention relates to a synthesis method of 2-[2-(2,4-diflurophenyl)-2-propylene-1-yl]-1,3-propyl glycol. The synthesis method comprises the following steps: mixing 3-chloro-1,2-propyl glycol with 1,3-difluorphenyl, adding a catalyst, reacting for 6-10 hours at room temperature, heating to 50-70 DEG C, and reacting for 2-4 hours; adding obtained mixture into hydrochloric acid solution at the temperature ranging from -5 DEG C to 5 DEG C, uniformly stirring, extracting for 3-5 times by taking dichloromethane as an extracting agent, and washing extract liquor once with saturated NaHCO3 solution, water and saturated saline solution; drying with anhydrous Na2SO4 and filtering, and evaporating dichloromethane to obtain 1-chloro-2-(2,4-diflurophenyl)-3-propyl glycol; adding 1-chloro-2-(2,4-diflurophenyl)-3-propyl glycol and potassium hydrogen sulphate into chlorobenzene, heating and refluxing for 10-16 hours; washing to be neutral, drying with anhydrous Na2SO4, then filtering, dissolving a distillation product into DMSO, adding diethyl malonate and hydroxide, reacting, and then carrying out reaction on the obtained products with lithium chloride and sodium borohydride, so that the target product is obtained, wherein a synthesis route is described in the specification.

Synthesis method of 1-(1-chloromethylvinyl)-2,4-difluorobenzene

The invention relates to a synthesis method of 1-(1-chloromethylvinyl)-2,4-difluorobenzene. The synthesis method of 1-(1-chloromethylvinyl)-2,4-difluorobenzene is characterized in that the synthesis method comprises the following steps: (1) mixing 2-chloromethyl epoxy propane with 1,3-difluorobenzene to perform reaction under an effect of catalyst to obtain 2-(2,4-diflurophenyl)-1-chloro-3-propanol; (2) mixing 2-(2,4-diflurophenyl)-1-chloro-3-propanol obtained in step (1) with potassium hydrogen sulfate and chlorobenzene to perform reaction to obtain a target product 1-(1-chloromethylvinyl)-2,4-difluorobenzene; a synthesis route is as shown in the accompanying drawing.

Synthesis method of 2-[2-(2,4-diflurophenyl)propenyl]-1,3-diethyl malonate

The invention relates to a synthesis method of 2-[2-(2,4-diflurophenyl)propenyl]-1,3-diethyl malonate. The synthesis method of 2-[2-(2,4-diflurophenyl)propenyl]-1,3-diethyl malonate is characterized in that the synthesis method comprises the following steps: (1) mixing 2-chloromethyl epoxy propane with 1,3-difluorobenzene to perform reaction under an effect of catalyst to obtain 2-(2,4-diflurophenyl)-1-chloro-3-propanol; (2) mixing 2-(2,4-diflurophenyl)-1-chloro-3-propanol obtained in step (1) with potassium hydrogen sulfate and chlorobenzene to perform reaction to obtain 1-(1-chloromethylvinyl)-2,4-difluorobenzene; (3) enabling 1-(1-chloromethylvinyl)-2,4-difluorobenzene obtained in step (2) to react with diethyl malonate to obtain a target product 2-[2-(2,4-diflurophenyl)propenyl]-1,3-diethyl malonate; a specific synthesis route is as shown in the accompanying drawing.

Method for synthesizing 2-methyl propionate-[(2S)-4-(2,4-diflurophenyl)-2-hydroxymethyl-4-amylene-1-group] ester

The invention provides a method for synthesizing 2-methyl propionate-[(2S)-4-(2,4-diflurophenyl)-2-hydroxymethyl-4-amylene-1-group] ester.The method includes the steps that 1,2,3-trichloropropane is added dropwise to 1,3-difluorobenzene, and aluminum trichloride is added for a reaction; the mixture is added to a hydrochloric acid solution for extraction, and washing is conducted with a saturated NaHCO3 solution, water and saturated salt solution in sequence; anhydrous Na2SO4 is used for drying and filtering, evaporation is conducted for solvent removal, and 1,3-dichloro-2-(2,4-diflurophenyl) propane is obtained; 1,3-dichloro-2-(2,4-diflurophenyl) propane and potassium hydroxide are added to tert butyl alcohol, and reflux is conducted for 3.5-6 h; tert butyl alcohol is removed, ice water is added, the mixture is neutralized with hydrochloric acid at the temperature of 5 to -5 DEG C to be neutral, dichloromethane is used for three times of extraction, anhydrous Na2SO4 is used for drying and filtering, a distillation product is dissolved in DMSO, a product obtained after diethyl malonate and diethyl malonate react are added and a product obtained after lithium chloride and sodium borohydride react are added and dissolved in methylbenzene, and sodium bicarbonate, Novo SP 435 esterifying enzymes and isobutyric anhydride are added for a reaction; the target product is obtained after washing, crystallization and drying are conducted.The synthesis path is shown in the description.

Synthesizing method of 1-(1-chloromethyl vinyl)-2, 4-difluorobenzene

The invention discloses a synthesizing method of 1-(1-chloromethyl vinyl)-2, 4-difluorobenzene. The synthesizing method includes: dripping 1, 2, 3-trichloropropane into 1, 3-difluorobenzene, and adding aluminum trichloride after 20-40 minutes; reacting for 0.5-1.5 hours under -5-5 DEG C, and heating to 20-45 DEG C for reaction for 1.5-3 hours; adding into hydrochloric acid solution for extraction, and sequentially washing with saturated NaHCO3 solution, water and saturated salt solution; drying with anhydrous Na2SO4, filtering, and evaporating to remove solvent so as to obtain 1, 3-dichloro-2-(2, 4-difluorophenyl) propane; adding the 1, 3-dichloro-2-(2, 4-difluorophenyl) propane and potassium hydroxide into tert-butyl alcohol for refluxing for 3.5-6 hours; removing the tert-butyl alcohol, adding ice water, neutralizing with hydrochloric acid under -5-5 DEG C until the product is neutral, extracting with dichloromethane for three times, drying with anhydrous Na2SO4, filtering, and evaporating to remove dichloromethane so as to obtain the target product. The path is shown as follows.

Method for synthesizing diethyl 2-[2-(2,4-difluorophenyl)allyl]-1,3-malonate

The invention relates to a method for synthesizing diethyl 2-[2-(2,4-difluorophenyl)allyl]-1,3-malonate. The method comprises the following steps: dropwisely adding 1,2,3-trichloropropane into 1,3-difluorobenzene, adding aluminum trichloride, extracting and washing; drying with anhydrous Na2SO4, filtering, evaporating to obtain 1,3-dichloro-2-(2,4-difluorophenyl)propane, adding the 1,3-dichloro-2-(2,4-difluorophenyl)propane and potassium hydroxide into an alcohol, and refluxing; removing the alcohol, adding ice water, neutralizing with hydrochloric acid at 5 to -5 DEG C, extracting with dichloromethane three times, drying with anhydrous Na2SO4, filtering, adding the obtained 1-chloro-2-(2,4-difluorophenyl)-3-propanol and potassium hydrogen sulfate into chlorobenzene, and heating under reflux; washing with water to a neutral state, drying with anhydrous Na2SO4, filtering to obtain 1-(1-chloromethylvinyl)-2,4-difluorobenzene, dissolving the 1-(1-chloromethylvinyl)-2,4-difluorobenzene in DMSO (dimethyl sulfoxide), adding diethyl malonate and hydroxide to react, extracting, washing, and carrying out reduced pressure distillation to obtain the target product. The synthesis route is disclosed in the specification.

Method for synthesizing 2-[2-(2,4-difluorophenyl)-2-propylene-1-yl]-1,3-propylene glycol

The invention discloses a method for synthesizing 2-[2-(2,4-difluorophenyl)-2-propylene-1-yl]-1,3-propylene glycol. The method comprises the following steps: dropwise adding 1,2,3-trichloropropane into 1,3-difluorobenzene; 20-40min later, adding aluminium trichloride; keeping reactions for 0.5-1.5h at 5-(-5) DEG C; heating to 20-45 DEG C and keeping reactions for 1.5-3h; adding the product into a hydrochloric acid solution and extracting; washing once using saturated NaHCO3 solution, water and saturated saline solution in sequence; drying with anhydrous Na2SO4 and filtering; evaporating to remove the solvent to obtain 1,3-dichloro-2-(2,4-difluorophenyl)propane; adding 1,3-dichloro-2-(2,4-difluorophenyl)propane and potassium hydroxide into tert-butyl alcohol, and enabling backflow for 3.5-6h; removing the tert-butyl alcohol; adding ice water and neutralizing to neutrality using hydrochloric acid at 5-(-5) DEG C; extracting using dichloromethane for three times; drying using anhydrous Na2SO4 and filtering; dissolving the evaporation and distillation product in DMSO, and adding diethyl malonate and hydroxide for reactions; and enabling the obtained product to react with lithium chloride and sodium borohydride to obtain a target product, wherein the synthesis path is shown in the specification.

Concise Synthesis of 1,3-Diacetoxy-2-[2′-(2′′,4′′-difluorophenyl)prop-2′-en-1′-yl]propane: An Intermediate for Posaconazole

A concise process of 1,3-diacetoxy-2-[2′-(2″,4″-difluorophenyl)prop-2′-en-1′-yl]propane has been developed. Diethyl malonate was C-alkylated with 2,3-dichloropropene and then the ester groups were reduced by LiAlH4 followed by acylation to provide 2-(2′-chloroprop-2′-en-1′-yl)-1,3-diacetoxypropane. The chloropropene was finally coupled with 2,4-difluorophenylmagnesium bromide and catalyzed by Fe(acac)3 to afford the title compound in good total yield. GRAPHICAL ABSTRACT.