Methyl Difluoro(fluorosulfonyl)acetate

• Catalog: OFC680159
• CAS: 680-15-9
• Category: Trifluoromethylation Agents
• Synonyms: Difluoro(fluorosulfonyl)acetic Acid Methyl Ester; Methyl (Fluorosulfonyl)difluoroacetate
• Purity: >97.0%(GC)
• MDL Number: MFCD00144316

• IUPAC Name: methyl 2,2-difluoro-2-fluorosulfonylacetate
• InChI: InChI=1S/C3H3F3O4S/c1-10-2(7)3(4,5)11(6,8)9/h1H3
• InChI Key: GQJCAQADCPTHKN-UHFFFAOYSA-N
• Isomeric SMILES: COC(=O)C(F)(F)S(=O)(=O)F
• EC Number: 629-185-1
• Reaxys Registry Number: 1812896

• Molecular Formula: C3H3F3O4S
• Molecular Weight: 192.11
• Boiling Point: 118 °C
• Flash Point: 47 °C
• Specific Gravity: 1.52
• Refractive Index: 1.35
• Appearance: Colorless to almost colorless clear liquid
• Storage: Store under inert gas
• Stability: Moisture sensitive

• XLogP3-AA: 0.8
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 7
• Rotatable Bond Count: 3
• Exact Mass: 191.97041423 g/mol
• Monoisotopic Mass: 191.97041423 g/mol
• Topological Polar Surface Area: 68.8Ų
• Heavy Atom Count: 11
• Formal Charge: 0
• Complexity: 250

Case Study

In Situ Generation of Difluoromethylene Ylides Using Methyl Difluoro(fluorosulfonyl)acetate for the Synthesis of 1,1-Difluoroalkenes

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

Methyl difluoro(fluorosulfonyl)acetate (MDFA) serves as an efficient in situ difluorocarbene precursor for the generation of difluoromethylene triphenylphosphonium ylide. Under nitrogen atmosphere, acetonitrile was heated to 70 °C in a flame-dried flask. Triphenylphosphine, potassium iodide, and 4-bromobenzaldehyde were sequentially added and stirred for 30 minutes before slow addition of MDFA. The iodide-induced demethylation of MDFA released difluorocarbene, which reacted with triphenylphosphine to form the ylide. The resulting ylide underwent a Wittig-type reaction with the aldehyde to furnish 1,1-difluoroalkenes. Following a 3-hour reaction, the mixture was quenched with water, extracted with ethyl acetate, and analyzed by ¹⁹F NMR using trifluorotoluene as internal standard, giving a crude yield of 72%. Residual triphenylphosphine was removed by repeated hexane washes.

Trifluoromethylation of 1-Aryl-4-Iodo-1,2,3-Triazoles Using Methyl Difluoro(fluorosulfonyl)acetate

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

Methyl Difluoro(fluorosulfonyl)acetate (MDFA) was employed as a key trifluoromethylating agent in a copper(I)-catalyzed transformation of 1-aryl-4-iodo-1,2,3-triazoles. In a representative synthesis of compound 6a, 4-(5-chloro-2-(4-iodo-1H-1,2,3-triazol-1-yl)phenyl)-6-methoxypyrimidine (5a, 30 g) was reacted with CuI (18 g) and tetrabutylammonium iodide (TBAI, 18 g) in hexamethylphosphoramide (HMPA, 240 mL) at 80 °C. MDFA (64.6 mL) was added dropwise, and the reaction proceeded at 90 °C for 2 hours. Upon completion (TLC-monitored), the mixture was quenched with water and extracted using ethyl acetate. After workup, the product was purified via silica gel chromatography (petroleum ether/ethyl acetate 8:2), yielding 11.2 g of the trifluoromethylated triazole derivative (6a) in 43.6% yield. This method demonstrated broad functional group tolerance and scalability, highlighting the practical utility of MDFA in heteroaryl trifluoromethylation.