Triethylamine → 1-Difluoromethoxy-4-{3-[3-(2-fluoro-ethyl)-cyclobutyl]phenyl-ethynyl}benzene

Participants

Reaction Steps

{3-[3-(2-Fluoro-ethyl)-cyclobutyl]-phenylethynyl}-triisopropyl-silane (349 mg, 0.973 mmol) was dissolved in THF (2 ml) and treated with a 1M solution of tetrabutylammonium fluoride (TBAF) in THF (2 ml) at room temperature. The crude product obtained from aqueous work-up was placed in a CEM snap top microwave vial and combined with 1-Bromo-4-Difluoromethoxybenzene (300 mg 1.30 mmol), copper iodide (35 mg, 0.131 mmol), tetrakis(triphenylphosphine)palladium (70 mg, 0.060 mmol) and triethylamine (4.3 g, 42.5 mmol). The vial was quickly agitated then irradiated in a CEM Explorer™ microwave instrument for 30 minutes at 80° C. Purification by column chromatography (gradient; 0%, then 5% EtOAc in hexanes) afforded an oil 178 mg (53%). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.68-1.80 (m, 2H) 1.85-2.11 (m, 2H) 2.17-2.36 (m, 2H) 2.38-2.43 (m, 1H) 3.28-3.65 (m, 1H) 4.24-4.52 (m, 2H) 7.01-7.47 (m, 5H) 7.18 (d, J=8.8 Hz, 2H) 7.58 (d, J=8.8 Hz, 2H).

Provenance & Evidence