Tetrahydrofuran → 5-Ethynyl-2-methylpyridine

Participants

Reaction Steps

To a NMP solution (20 mL) of 5-bromo-2-methyl-pyridine (1.0 g) were added trimethylsilylacetylene (1.2 mL), tetrakis(triphenylphosphine)palladium(0) (130 mg), copper(I) iodide (44 mg), and N,N-diisopropylethylamine (2.0 mL), which was stirred under a nitrogen atmosphere for 2 hours at 65° C. Water was added at room temperature to the reaction mixture, which was then extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate and filtered, after which the solvent was evaporated from the filtrate under a reduced pressure. The residue was purified by silica gel column chromatography (heptane:ethyl acetate=5:1) to obtain a mixture (810 mg) of 5-bromo-2-methyl-pyridine and 2-methyl-5-trimethylsilanylethynyl-pyridine. Then, to a solution of THF (10 mL) and ethanol (5 mL) of the mixture (810 mg) of 5-bromo-2-methyl-pyridine and 2-methyl-5-trimethylsilanylethynyl-pyridine was added potassium carbonate (1.2 g) at room temperature, which was stirred for 2 hours and 30 minutes at room temperature. Water was added at room temperature to the reaction mixture, which was then extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate, and filtered, after which the solvent was evaporated from the filtrate under a reduced pressure, and the residue was purified by silica gel column chromatography (heptane:ethyl acetate=5:1) to obtain the titled compound (55 mg).

Provenance & Evidence