Reacción #1515000

Ecuación de reacción

4-(adamantan-1-ylmethoxy)-3-bromobenzonitrile

potassium carbonate

(2-methoxypyridin-3-yl)boronic acid

→

title compound

Rendimiento 98.8%

4-(adamantan-1-ylmethoxy)-3-(2-methoxypyridin-3-yl)benzonitrile

Rendimiento 98.8%

Disolventes

dioxane

Condiciones de reacción

Tratamiento posterior

1. 1
   Otrowas degassed three times with nitrogen
2. 2
   Otrothe reaction mixture was degassed three further times with nitrogen
3. 3
   Temperaturathe reaction was cooled to ambient temperature
4. 4
   Otrothe reaction was degassed three times with nitrogen
5. 5
   Temperaturaheated at 90° C. for further 7 h
6. 6
   TemperaturaAfter cooling to ambient temperature
7. 7
   workup.ADDITIONthe reaction mixture was diluted with ethyl acetate (200 mL)
8. 8
   Lavadowashed with water and brine
9. 9
   Secadodried over anhydrous sodium sulfate
10. 10
    Concentraciónconcentrated in vacuo
11. 11
    OtroPurification of the residue by column chromatography (15% ethyl acetate in hexanes)

Procedimiento

A reaction mixture of 4-(adamantan-1-ylmethoxy)-3-bromobenzonitrile (1.04 g, 3.00 mmol), potassium carbonate (1.00 g, 7.20 mmol) and (2-methoxypyridin-3-yl)boronic acid (0.92 g, 6.00 mmol) in dioxane (30 mL) was degassed three times with nitrogen, then tetrakis(triphenylphosphine)palladium(0) (0.18 g, 0.15 mmol) was added and the reaction mixture was degassed three further times with nitrogen. The resulting mixture was heated at 90° C. for 19 h, and then the reaction was cooled to ambient temperature, (2-methoxypyridin-3-yr)boronic acid (0.46 g, 3.00 mmol) and tetrakis(triphenylphosphfne)-pailadium(0) (0.09 g, 0.08 mmol) were added and the reaction was degassed three times with nitrogen and heated at 90° C. for further 7 h. After cooling to ambient temperature, the reaction mixture was diluted with ethyl acetate (200 mL) and washed with water and brine; dried over anhydrous sodium sulfate and concentrated in vacuo. Purification of the residue by column chromatography (15% ethyl acetate in hexanes) afforded the title compound as a colorless solid (1.11 g, 98%): 1H NMR (300 MHz, CDCl3) δ 8.20-8.16 (m, 1H), 7.62-7.48 (m, 3H), 6.96-6.91 (m, 2H), 3.87 (s, 3H), 3.48 (s, 2H), 1.89 (br s, 3H), 1.68-1.35 (m, 12H); MS (ES+) m/z: 375.2, (M+1).

Fuente