Difluoromethyl Trifluoromethanesulfonate

• Difluoromethyl Trifluoromethanesulfonate [T4382]
• 2-Nitrophenol [N0219]
• Potassium Hydroxide
• Acetonitrile
• Water

6 mol/L Potassium hydroxide aqueous solution (1.0 mL, 6 mmol) was added to a solution of 2-nitrophenol (70 mg, 0.50 mmol) in acetonitrile (1.0 mL) and stirred vigorously at room temperature. Then, difluoromethyl trifluoromethanesulfonate (300 mg, 1.50 mmol) was added to the mixture in one shot and stirred vigorously for 2 minutes at room temperature. The reaction mixture was extracted with diethyl ether (10 mL x 2), dried over sodium sulfate (10 g), and concentrated under reduced pressure to afford 1-(difluoromethoxy)-2-nitrobenzene (93.3 mg, 98% yield) as a colorless oil.

• The reaction was monitored by TLC (hexane:ethyl acetate = 3:1, Rf = 0.5) and UPLC-MS.
• This reagent is highly volatile, so prompt handling was required.
• Since high-purity product was obtained after the completion of separation process, no further purification steps were required.

1-(Difluoromethoxy)-2-nitrobenzene

¹H NMR (400 MHz, CDCl₃); δ 7.93 (d, J = 8.0 Hz, 1H),　7.63 (t, J = 7.2 Hz, 1H), 7.40 (m, 2H), 6.63 (t, J = 73.2 Hz, 1H)

• Synthesis of Difluoromethyl Ethers with Difluoromethyltriflate
  • P. S. Fier, J. F. Hartwig, Angew. Chem. Int. Ed. 2013, 52, 2092.