Chemical Properties
clear colorless liquid
Uses
3,5-Difluoroanisole is used in the preparation of indazole arylsulfonamides as allosteric CC-chemokine receptor 4 antagonists. Also used in the preparation of imidazo[1,5-a]pyrido[3,2-e]pyrazines and imidazo[1,5-a]quinoxalines as orally active phosphodiesterase 10A inhibitors.
General Description
The structure and vibrations of 3,5-difluoroanisole in first electronically excited state were studied by mass-analyzed resonant two-photon ionization technique as well as the quantum chemical calculations.
Synthesis
To a stirred suspension of 3,5-difluorophenol (12.5 g, 96 mmol) and potassium carbonate (66.0 g, 480 mmol) in acetone (400 mL) was added methyl iodide (27 mL, 480 mmol) in a single addition. The reaction mixture was then heated to reflux at 60 °C for 18 hours. After cooling to room temperature, the excess solvent was evaporated under reduced pressure, 150 mL of water was added and extracted with ether (2 x 300 mL). The combined organic layers were washed sequentially with 0.1 M sodium hydroxide solution (100 mL) and water (100 mL), dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure to give 3,5-difluoroanisole (12.0 g, 80% yield) as a colorless oil.1H-NMR (400 MHz, CDCl3) δppm: 3.81 (s, 3H), 6.43- 6.46 (m, 3H).
References
[1] Tetrahedron Letters, 2004, vol. 45, # 1, p. 95 - 98
[2] Patent: WO2017/221092, 2017, A1. Location in patent: Paragraph 00138
[3] Patent: WO2017/221100, 2017, A1. Location in patent: Paragraph 00140
[4] Patent: US6149990, 2000, A
