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

Temperature

85 °C

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).

1. temperaturecooled to room temperature
2. washThe mixture was washed with a 10% aqueous solution of lithium chloride (2×100 mL)
3. washwashed with a 2M aqueous solution of ammonium hydroxide (100 mL)
4. washwashed with brine
5. dry with materialdried over anhydrous sodium sulfate
6. concentrationConcentration
7. customfollowed by purification by silica gel chromatography with hexanes/ethyl acetate (3/2)

ORD record

ord-16671943b4b04e349182898ddc3fe349

Source dataset

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08404672B2