Reacción #2275694

Ecuación de reacción

3,5-dichloro-2-cyanopyridine

benzyl alcohol

sodium hydride

hydrogen

→

desired compound

Rendimiento 94.0%

3,5-bis-benzyloxy-pyridine-2-carbonitrile

Rendimiento 94.0%

Disolventes

THF

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturato warm to room temperature
2. 2
   TemperaturaThe solution is re-cooled to 0° C.
3. 3
   Otrois transferred to an unfocussed Mars 5 CEM microwave reactor to 190° C.
4. 4
   OtroThe reaction mixture is quenched with H2O
5. 5
   Concentraciónconcentrated under reduced pressure
6. 6
   workup.ADDITIONdiluted with EtOAc
7. 7
   Lavadowashed with 2M Na2CO3, H2O and saturated aqueous NaCl
8. 8
   SecadoThe organic layer is dried (MgSO4)
9. 9
   Filtraciónfiltered
10. 10
    Concentraciónconcentrated under reduced pressure
11. 11
    Otroto give a brown solid
12. 12
    OtroThe crude solid is purified over silica (EtOAc:heptane, gradient 1:1 to 1:0)

Procedimiento

To an 80 mL microwave pressure vessel is charged dry THF (30 mL) and benzyl alcohol (6.32 mL, 61.1 mmol). The solution is cooled to 0° C. and sodium hydride (2.44 g of a 60% dispersion in mineral oil, 61.1 mmol) is added in portions. The reaction mixture is gradually allowed to warm to room temperature with efficient stirring until the evolution of hydrogen gas ceases. The solution is re-cooled to 0° C. and 3,5-dichloro-2-cyanopyridine (5.00 g, 29.1 mmol) is added, and the solution is transferred to an unfocussed Mars 5 CEM microwave reactor to 190° C., 300 W and held for 5 hours. The reaction mixture is quenched with H2O, concentrated under reduced pressure, diluted with EtOAc and washed with 2M Na2CO3, H2O and saturated aqueous NaCl. The organic layer is dried (MgSO4), filtered and concentrated under reduced pressure to give a brown solid. The crude solid is purified over silica (EtOAc:heptane, gradient 1:1 to 1:0) to afford 8.6 g (94% yield) of the desired compound as an orange solid. 1H NMR (400 MHz, CDCl3) δ ppm 7.96 (1H, d, J=2.2 Hz), 7.25-7.37 (10H, m), 6.78 (1H, d, J=2.2 Hz), 5.10 (2H, s), 5.03 (2H, s). HPLC-MS: m/z 317 [M+H]+.

Fuente