4-Cyanophenol → 4-[(2-Methylbut-3-yn-2-yl)oxy]benzonitrile

Participants

Reaction Conditions

Reaction Steps

To a solution of 4-cyanophenol (9.0 g, 75.55 mmol, commercially available) and anhydrous acetonitrile (120 mL) at ~0° C. under argon was added 1,8-diazabicyclo-[5.4.0]undec-7-ene (DBU, 14.0 mL, 93.61 mmol, 1.24 eq based on the input of 4-cyanophenol). A temperature increase to 12.6° C. was observed. After the solution had cooled to 0° C., copper bronze (cooper powder, 49.8 mg, 0.783 mmol, 0.0104 eq, 1.04 mol %) was added followed by the addition of a portion of the cuprous chloride in acetonitrile solution prepared above (600 μL, 15.49 μmole, 0.000205 eq., 0.0205 mol %). To the resulting mixture was added, dropwise over 12 minutes, 3-chloro-3-methyl-1-butyne (7.03 g, 68.54 mmol, 0.907 eq. based on the input of 4-cyanophenol). The resulting mixture was allowed to stir at 0° C. under argon. After stirring for 10 hours, the reaction mixture was filtered through a small pad of Celite (to remove the remaining copper bronze) using additional acetonitrile to complete the transfer and to wash the filter bed. The filtrate was concentrated at reduced pressure (bath temperature 40° C.) and the residue was partitioned between 1N HCl (100 mL) and toluene (400 mL). The organic fraction was washed with 1N HCl (2×60 mL), 1N NaOH (2×60 mL), and brine. After drying (magnesium sulfate), the solvent was removed at reduced pressure to give crude title compound as a pale yellow oil (10.68 g). Distillation of the crude material (bulb-to-bulb, ~70°-90° C., ~0.15 mm Hg) afforded the title compound as a colorless, low melting (mp 28°-29° C.) solid (10.40 g).

Provenance & Evidence