2-Methyl-3-butyn-2-ol → 2-methyl-4-(3-pyridinyl)-3-butyn-2-ol

Temperature

0 °C

3-Bromopyridine (3.0 mL, 31 mmol), triethylamine (22 mL, 160 mmol), CuI (1.2 g, 6.2 mmol), and PdC2(PPh3)2 (1.1 g, 1.5 mmol) were combined in DME (92 mL) and cooled to 0° C. 2-Methyl-3-butyne-2-ol (9.0 mL, 93 mmol) was then added and the reaction was allowed to slowly warm to ambient temperature. The mixture was then heated to 55-60° C. for 16 h. The mixture was filtered through Celite™, and the pad was washed thoroughly with ethyl acetate. The combined filtrates were washed with brine (3×100 mL), dried over MgSO4, and filtered. The solution was concentrated in vacuo, and the residue was purified by column chromatography eluting with 90:10 hexane:ethyl acetate then ethyl acetate to afford 2-methyl-4-(3-pyridinyl)-3-butyn-2-ol (2.0 g; 40% yield) as a brown oil 1H NMR (CDCl3, 300 MHz) δ 8.76 (br s, 1H), 8.52 (br s, 1H), 7.74-7.70 (m, 1H), 4.08 (br s, 1H), 1.63 (s, 3H). MS (EI ionization) 161 (M+).

1. temperatureto slowly warm to ambient temperature
2. temperatureThe mixture was then heated to 55-60° C. for 16 h
3. filtrationThe mixture was filtered through Celite™
4. washthe pad was washed thoroughly with ethyl acetate
5. washThe combined filtrates were washed with brine (3×100 mL)
6. dry with materialdried over MgSO4
7. filtrationfiltered
8. concentrationThe solution was concentrated in vacuo
9. customthe residue was purified by column chromatography
10. washeluting with 90:10 hexane

ORD record

ord-42a9547ae70e4c7eb7c5feb9d384dd6e

Source dataset

uspto-grants-2004_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06774138B2