Methyl 2,2-difluoro-2-(fluorosulfonyl)acetate

• Catalog: OFC680159-4
• CAS: 680-15-9
• Category: Other Fluorinated Group Introducing Agents
• Synonyms: methylfluorosulphonyldifluoroacetate; Methyl difluoro(fluorosulfonyl)acetate; MFSDA; 氟磺酰二氟乙酸甲酯

• InChI: InChI=1S/C3H3F3O4S/c1-10-2(7)3(4,5)11(6,8)9/h1H3
• InChI Key: GQJCAQADCPTHKN-UHFFFAOYSA-N
• Canonical SMILES: COC(=O)C(F)(F)S(=O)(=O)F

• Molecular Formula: C3H3F3O4S
• Molecular Weight: 192.114
• Boiling Point: 118.0 °C
• Density: 1.516 g/cm3
• Refractive Index: 1.35
• Appearance: Colorless to yellowish liquid
• Solubility: Unknown.

• Exact Mass: 191.9704

Case Study

Synthetic Application of Methyl 2,2-Difluoro-2-(Fluorosulfonyl)Acetate as a Trifluoromethylation Reagent

Panja C, et al. Journal of Fluorine Chemistry, 2020, 236, 109516.

Methyl 2,2-difluoro-2-(fluorosulfonyl)acetate (MDFA) serves as a versatile trifluoromethylation reagent, particularly useful in synthesizing 1-aryl-4-(trifluoromethyl)-1H-1,2,3-triazoles. MDFA is able to be a potent source of difluorocarbene at higher temperatures.
General Procedure for Synthesizing 1-Aryl-4-(trifluoromethyl)-1H-1,2,3-triazole
To synthesize 1-aryl-4-(trifluoromethyl)-1H-1,2,3-triazole, a solution of 4-iodo-substituted-aryl-1H-1,2,3-triazole (1.5 mmol) in hexamethylphosphoramide (HMPA) (15 mL) is prepared and heated to 80 °C. Copper(I) iodide (CuI) (1.95 mmol) and tetrabutylammonium iodide (0.75 mmol) are added to the solution, followed by the dropwise addition of MDFA (10.5 mmol) over 5 minutes. The reaction mixture is then stirred at 90 °C for 2 hours, with progress monitored by TLC (8:2, petroleum ether: ethyl acetate).
After the reaction, the mixture is cooled to room temperature and quenched with ice-cold water (15 mL), then diluted with ethyl acetate (15 mL) and filtered through a celite bed. The celite bed is washed with ethyl acetate (7.5 mL). The organic layer is separated, washed with water (7.5 mL) and brine solution (7.5 mL), dried over anhydrous sodium sulfate, and filtered. The filtrate is concentrated to obtain the crude product.
The crude material is purified by column chromatography on silica gel using petroleum ether/ethyl acetate (8:2) as the eluent, yielding the pure 1-aryl-4-(trifluoromethyl)-1H-1,2,3-triazole.

Methyl 2,2-Difluoro-2-(Fluorosulfonyl)Acetate as a Source of Difluorocarbin for the Synthesis of 1,1-Difluoroalkenes

Charles S. Thomoson CS, et al. Journal of Fluorine Chemistry, 2013, 150, 53-59.

Methyl 2,2-difluoro-2-(fluorosulfonyl)acetate (MDFA) is an excellent source of difluorocarbenes. These difluorocarbenes react with triphenylphosphine to form difluoromethylene triphenylphosphonium ylide. In the presence of an aldehyde or an active ketone, this ylide further reacts to produce 1,1-difluoroalkenes.
Typical Procedure for the Preparation of 1,1-Difluoroalkenes
1.Equip a 250 mL, three-necked round-bottom flask with a stir bar. Fit the vessel with a condenser topped by a T-tube with a slow flow of N₂, and seal with septa. Flame dry the vessel and allow it to cool to room temperature.
2.Under an inert nitrogen atmosphere, add acetonitrile (75 mL) to the vessel and increase the temperature to 70 °C.
3.Add triphenylphosphine (34.5 g, 135 mmol, 3 equiv.), potassium iodide (15.0 g, 90 mmol, 2 equiv.), and 4-bromobenzaldehyde (9.80 g, 45 mmol, 1 equiv.), and stir for 30 minutes.
4.Slowly add MDFA (19.7 g, 78.75 mmol, 1.75 equiv.) over 1 hour. Stir the resulting mixture for three hours, maintaining a nitrogen atmosphere until the reaction is complete.
5.Quench the reaction with water and extract with ethyl acetate. Add trifluorotoluene (15 mmol) as an internal standard and measure the yield of the crude reaction by ¹⁹F NMR.
6.Remove the ethyl acetate by rotary evaporation to produce a black, semi-solid slurry. Isolate the product from the slurry and separate it from residual triphenylphosphine by extracting five times with hexane (100 mL).
7.Combine and concentrate the hexane extracts. Remove additional impurities via column chromatography using a 95:5 mixture of hexanes:chloride to obtain the pure product.