反応 #2275694

反応方程式

3,5-dichloro-2-cyanopyridine

benzyl alcohol

sodium hydride

hydrogen

→

desired compound

収率 94.0%

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

収率 94.0%

溶媒

THF

反応条件

後処理

1. 1
   温度to warm to room temperature
2. 2
   温度The solution is re-cooled to 0° C.
3. 3
   その他is transferred to an unfocussed Mars 5 CEM microwave reactor to 190° C.
4. 4
   その他The reaction mixture is quenched with H2O
5. 5
   濃縮concentrated under reduced pressure
6. 6
   workup.ADDITIONdiluted with EtOAc
7. 7
   洗浄washed with 2M Na2CO3, H2O and saturated aqueous NaCl
8. 8
   乾燥The organic layer is dried (MgSO4)
9. 9
   ろ過filtered
10. 10
    濃縮concentrated under reduced pressure
11. 11
    その他to give a brown solid
12. 12
    その他The crude solid is purified over silica (EtOAc:heptane, gradient 1:1 to 1:0)

実験手順

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]+.

出典