Réaction #2275694

Équation de réaction

3,5-dichloro-2-cyanopyridine

benzyl alcohol

sodium hydride

hydrogen

→

desired compound

Rendement 94.0%

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

Rendement 94.0%

Solvants

THF

Conditions de réaction

Traitement

1. 1
   Températureto warm to room temperature
2. 2
   TempératureThe solution is re-cooled to 0° C.
3. 3
   Autreis transferred to an unfocussed Mars 5 CEM microwave reactor to 190° C.
4. 4
   AutreThe reaction mixture is quenched with H2O
5. 5
   Concentrationconcentrated under reduced pressure
6. 6
   workup.ADDITIONdiluted with EtOAc
7. 7
   Lavagewashed with 2M Na2CO3, H2O and saturated aqueous NaCl
8. 8
   SéchageThe organic layer is dried (MgSO4)
9. 9
   Filtrationfiltered
10. 10
    Concentrationconcentrated under reduced pressure
11. 11
    Autreto give a brown solid
12. 12
    AutreThe crude solid is purified over silica (EtOAc:heptane, gradient 1:1 to 1:0)

Mode opératoire

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]+.

Source