Reacción #1605780

Ecuación de reacción

2-bromo-5-methylpyridine

acetonitrile

n-butyl lithium

→

2-(5-methylpyridin-2-yl) acetonitrile

Rendimiento 80.7%

Disolventes

THF

THF

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.WAITThe reaction mixture was kept at minus 78° C. for 1 hour
2. 2
   Temperaturawarmed up slowly to room temperature
3. 3
   workup.STIRRINGstirred for another hour
4. 4
   Otrothe layer was separated
5. 5
   LavadoThe organic layer was washed with water and brine
6. 6
   Secadodried over MgSO4
7. 7
   Filtraciónfiltered
8. 8
   Otroevaporated
9. 9
   Otroto give 18 g of crude product
10. 10
    OtroThe crude product was purified by silica-gel column chromatography (eluent, PE/EtOAc=15:1)

Procedimiento

To a solution of anhydrous acetonitrile (10.1 mL, 191.83 mmol, 3.3 equiv.) in dry THF (500 mL) was added dropwise n-butyl lithium (2.5 M in hexane, 69.8 mL, 174.39 mmol, 3 equiv.) at minus 78° C. under nitrogen atmosphere. The resulting white suspension was stirred at minus 78° C. for 1 hour, and then a solution of 2-bromo-5-methylpyridine (10.0 g, 58.13 mmol, 1 equiv.) in dry THF (30 mL) was added. The reaction mixture was kept at minus 78° C. for 1 hour and then warmed up slowly to room temperature and stirred for another hour. Ice water was added and the layer was separated. The organic layer was washed with water and brine, dried over MgSO4, filtered, and evaporated to give 18 g of crude product. The crude product was purified by silica-gel column chromatography (eluent, PE/EtOAc=15:1) to give 2-(5-methylpyridin-2-yl) acetonitrile (6.2 g, yield 80%). 1H NMR (300 MHz, CDCl3): δ 8.40 (d, J=3.0 Hz, 1H), 7.54 (dd, J1=3.0 Hz, J2=6.0 Hz, 1 H), 7.32 (d, J=6.0 Hz, 1 H), 3.90 (s, 2H), 2.40 (s, 3H).

Fuente