2-Bromopyridine → (3-Methylbut-1-ynyl)pyridine

Participants

Reaction Conditions

Reaction Steps

To a degassed solution of 2-bromopyridine (0.604 mL, 6.33 mmol), bis(triphenylphosphine)palladium(II) chloride (0.267 g, 0.380 mmol), copper (I) iodide (0.060 g, 0.316 mmol), and diisopropyldiethylamine (3.61 mL, 25.3 mmol) in N,N-dimethylformamide (20 mL) was added 3-methylbut-1-yne (0.647 g, 9.49 mmol). The reaction mixture was heated to 85° C. for 16 h, cooled to room temperature, and diluted with ethyl acetate (150 mL). The mixture was washed with a 10% aqueous solution of lithium chloride (2×100 mL), washed with a 2M aqueous solution of ammonium hydroxide (100 mL), washed with brine, and dried over anhydrous sodium sulfate. Concentration followed by purification by silica gel chromatography with hexanes/ethyl acetate (3/2) afforded (3-methylbut-1-ynyl)pyridine (696 mg, 4.65 mmol, 73% yield). The compound had an HPLC retention time=1.02 min.—Column: YMC COMBISCREEN® ODS-A 4.6×50 mm S-5; Gradient time: 4 min; Flow rate=4 ml/min; Solvent A=10% MeOH—90% Water—0.1% TFA; Solvent B=90% MeOH—10% water—0.1% TFA. LC-MS: M+1=146.32. 1H NMR (400 MHz, CDCl3) δ ppm 1.29 (s, 3H), 1.30 (s, 3H), 2.82 (dt, J=13.80, 6.90 Hz, 1H), 7.18 (dd, J=7.65, 4.89 Hz, 1H), 7.37 (d, J=7.78 Hz, 1H), 7.61 (td, J=7.72, 1.13 Hz, 1H), and 8.55 (d, J=4.77 Hz, 1H).

Provenance & Evidence