55039-89-9

Usage

Uses

Used in Pharmaceutical Industry:
2,2-Difluoropentan-4-enoic acid is used as a key intermediate for the synthesis of 5-hydroxy-3,3-difluoropiperidine, which is a compound with potential pharmaceutical applications. It is involved in the iodolactonization reaction to give the corresponding gamma-lactone, which is then converted to prepare the desired piperidine derivative.

Upstream product

• 116-14-3 polytetrafluoroethylene 
• 107-18-6 allyl alcohol 
• 113991-42-7 1,2,2-trifluorovinyl allyl ether 
• 118337-48-7 allyl chlorodifluoroacetate 
• 118373-18-5 trimethylsilyl 2,2-difluoro-4-pentenoate 

Downstream Products

• 110482-96-7 2,2-difluoro-4-pentenoic acid ethyl ester 
• 364049-82-1 N-(4-methoxyphenyl)-1-chloro-2,2-difluoro-4-pentenimidoyl chloride 
• 106745-96-4 N-<3,3-Difluoro-2-oxo-1-(phenylmethyl)-5-hexenyl>benzamide 
• 109004-86-6 4-Benzyl-4-(2,2-difluoro-pent-4-enoyl)-2-phenyl-4H-oxazol-5-one 
• 109004-87-7 N-(3,3-Difluoro-2-oxo-hex-5-enyl)-benzamide 
• 109005-03-0 N-(1-Benzyl-3,3-difluoro-2-oxo-hex-5-enyl)-acetamide 
• 109004-84-4 4-(2,2-Difluoro-pent-4-enoyl)-2-phenyl-4H-oxazol-5-one 
• 106745-97-5 6-Benzoylamino-4,4-difluoro-8-methyl-1-nonen-5-one 
• 109004-96-8 2,2-Difluoro-pent-4-enoic acid 4-benzyl-2-methyl-oxazol-5-yl ester 
• 109005-00-7 4-Benzyl-4-(2,2-difluoro-pent-4-enoyl)-2-methyl-4H-oxazol-5-one 
• 109004-85-5 4-(2,2-Difluoro-pent-4-enoyl)-4-isobutyl-2-phenyl-4H-oxazol-5-one 
• 109004-91-3 2,2-Difluoro-pent-4-enoic acid 4-isobutyl-2-phenyl-oxazol-5-yl ester 
• 109004-92-4 2,2-Difluoro-pent-4-enoic acid 4-benzyl-2-phenyl-oxazol-5-yl ester 
• 109005-01-8 N-[3,3-Difluoro-1-(4-nitro-benzyl)-2-oxo-hex-5-enyl]-benzamide 

Relevant academic research and scientific papers

Practical preparation of 3,3-difluoropyrrolidine

A practical and cost-effective synthesis of 3,3-difluoropyrrolidine is reported. The synthesis involves the isolation of two intermediates, which are prepared via two efficient through processes: (1) a Claisen rearrangement followed by a Ru(VIII)-catalyzed oxidation to prepare the 2,2-difluorosuccinic acid and (2) an efficient cyclization to form N-benzyl-3,3-difluoropyrrolidinone followed by BH3·Me2S reduction.

Process for the preparation of N-methyl-D-phenylalanyl-N-?1-?3-?(aminoiminomethyl)amino!propyl!-3,3-difluoro-2-oxohexyl!-L-prolinamide

The present invention relates to a novel process for preparing preparing N-methyl-D-phenylalanyl-N-?1-?3-?(aminoiminomethyl)amino!propyl!-3,3-difluoro-2-oxohexyl!-L-prolinamide or a pharmaceutically acceptable salt thereof and to a key intermediate by directly guanylating Dakin-West intermediates.

Fluorinated analogues as mechanistic probes in valproic acid hepatotoxicity: Hepatic microvesicular steatosis and glutathione status

It is postulated that the hepatotoxicity of valproic acid (VPA) results from the mitochondrial β-oxidation of its cytochrome P450 metabolite, 2- propyl-4-pentenoic acid (4-ene VPA), to 2-propyl-(E)-2,4-pentadienoic acid ((E)-2,4-diene VPA) which, in the CoA thioester form, either depletes GSH or produces a putative inhibitor of β-oxidation enzymes. In order to test this hypothesis, 2-fluoro-2-propyl-4-pentenoic acid (α-fluoro-4-ene VPA) which was expected to be inert to β-oxidative metabolism was synthesized and its effect on rat liver studied in comparison with that of 4-ene VPA. Similarly, the known hepatotoxicant 4-pentenoic acid (4-PA) and 2,2-difluoro-4-pentenoic acid (F2-4-PA) were compared. Male Sprague-Dawley rats (150-180 g, 4 rats per group) were dosed ip with 4-one VPA (0.7 mmol/kg per day), 4-PA (1.0 mmol/kg per day), or equivalent amounts of their α-fluorinated analogues for 5 days. Both 4-ene VPA and 4-PA induced severe hepatic microvesicular steatosis (> 85% affected hepatocytes), and 4-ene VPA produced mitochondrial alterations. By contrast, α-fluoro-4-ene VPA and F2-4-PA were not observed to cause morphological changes in the liver. The major metabolite of 4-ene VPA in the rat urine and serum was the β-oxidation product (E)-2,4-diene VPA. The N-acetylcysteine (NAC) conjugate of (E)-2,4-diene VPA was also found in the urine. Neither (E)-2,4-diene VPA nor the NAC conjugate could be detected in the rats administered α-fluoro-4-ene VPA. In a second set of rats (3 rats per group), total liver GSH levels were determined to be depleted to 56% and 72% of control following doses of 4-ene VPA (1.4 mmol/kg) and equivalent α-fluoro-4-ene VPA, respectively. Mitochondrial GSH remained unchanged in the α-fluoro-4-ene VPA treated group but was reduced to 68% of control in the rats administered 4-ene VPA. These results strongly support the theory that hepatotoxicity of 4-ene VPA, and possibly VPA itself, is mediated largely through β-oxidation of 4-ene VPA to reactive intermediates that are capable of depleting mitochondrial GSH.

Process for the preparation of 2,2-difluoropent-4-enoic acids and acid derivatives

The reaction of allyl bromo- or chloro-difluoroacetates with monochlorisilanes in the presence of zinc with heating gives silyl esters of α,α-difluoro-γ,δ-pentenoic acids. The free acids, from which acid derivatives can be prepared by conventional methods, are obtained by hydrolysis. The pentenoic acids and pentenoic acid derivatives are suitable for the preparation of polymers and copolymers, from which metal-organic polymers and copolymers having catalytic properties are obtainable.

FLUORINE-CONTAINING ORGANOZINC REAGENTS. V. THE REFORMATSKII-CLAISEN REACTION OF CHLORODIFLUOROACETIC ACID DERIVATIVES

Silicon induced Reformatskii-Claisen reaction of allyl chlorodifluoroacetate (1) affords 2,2-difluoro-4-pentenoic acid (2) in good yields.Starting from inexpensive chlorodifluoroacetic acid, a variety of useful fluorine-containing synthetic building block

Synthesis and Evaluation of Phospholipid Analogues as Inhibitors of Cobra Venom Phospholipase A2

Analogues of phospholipids that contain fluoro ketone, ketone, and alcohol replacements for the ester at the 2-position of the glycerol backbone have been prepared and analyzed as inhibitors of phospholipase A2 from Naja naja naja venom.Phospholipid analogues were studied that contain two alkyl chains as well as single chain compounds that lack carbon-1 of the glycerol backbone and the attached acyl unit.Compounds that contain both long and medium length alkyl chains were studied.All of the potential inhibitors were tested in a well-defined mixed micelle system in which both the substrates and the inhibitors have been incorporated into Triton X-100 micelles.Surprisingly, the best inhibitors studied were the single chain fluoro ketones despite the fact that the enzyme has a strong preference for two-chain lipids.The most potent compound was found to have a dissociation constant some 600-3000-fold lower than the Michaelis constant for dipalmitoyl phosphatidylcholine substrate. 19F NMR studies of the fluoro ketone phospholipid analogues in micelles show that whereas the single chain compounds are partially in the hydrated-ketone form, the two-chain compounds are less than 0.1percent hydrated.In every case studied, potent inhibition of phospholipase A2 was observed only with those compounds that are significantly hydrated in the micelle, and it is suggested that the hydrated fluoro ketone containing phospholipid analogues are the species responsible for the inhibition.In addition, the single chain fluoro ketones were better inhibitors than single and double chain alcohol and ketone analogues.Previous studies have been show that the cobra venom enzyme is activated by choline-containing lipids, and evidence is presented for the binding of the hydrated fluoro ketone inhibitors selectively to the activated enzyme.