Reaktion #2275694

Reaktionsgleichung

3,5-dichloro-2-cyanopyridine

benzyl alcohol

sodium hydride

hydrogen

→

desired compound

Ausbeute 94.0%

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

Ausbeute 94.0%

Lösungsmittel

THF

Reaktionsbedingungen

Aufarbeitung

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

Vorschrift

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]+.

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