Реакция #2275694

Уравнение реакции

3,5-dichloro-2-cyanopyridine

benzyl alcohol

sodium hydride

hydrogen

→

desired compound

Выход 94.0%

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

Выход 94.0%

Растворители

THF

Условия реакции

Обработка

1. 1
   Температураto warm to room temperature
2. 2
   ТемператураThe solution is re-cooled to 0° C.
3. 3
   Другоеis transferred to an unfocussed Mars 5 CEM microwave reactor to 190° C.
4. 4
   ДругоеThe reaction mixture is quenched with H2O
5. 5
   Концентрированиеconcentrated under reduced pressure
6. 6
   workup.ADDITIONdiluted with EtOAc
7. 7
   Промывкаwashed with 2M Na2CO3, H2O and saturated aqueous NaCl
8. 8
   СушкаThe organic layer is dried (MgSO4)
9. 9
   Фильтрацияfiltered
10. 10
    Концентрированиеconcentrated under reduced pressure
11. 11
    Другоеto give a brown solid
12. 12
    ДругоеThe crude solid is purified over silica (EtOAc:heptane, gradient 1:1 to 1:0)

Методика

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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