반응 #2275694

반응 방정식

3,5-dichloro-2-cyanopyridine

benzyl alcohol

sodium hydride

hydrogen

→

desired compound

수율 94.0%

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

수율 94.0%

용매

THF

반응 조건

후처리

1. 1
   온도to warm to room temperature
2. 2
   온도The solution is re-cooled to 0° C.
3. 3
   기타is transferred to an unfocussed Mars 5 CEM microwave reactor to 190° C.
4. 4
   기타The reaction mixture is quenched with H2O
5. 5
   농축concentrated under reduced pressure
6. 6
   workup.ADDITIONdiluted with EtOAc
7. 7
   세척washed with 2M Na2CO3, H2O and saturated aqueous NaCl
8. 8
   건조The organic layer is dried (MgSO4)
9. 9
   여과filtered
10. 10
    농축concentrated under reduced pressure
11. 11
    기타to give a brown solid
12. 12
    기타The crude solid is purified over silica (EtOAc:heptane, gradient 1:1 to 1:0)

실험 절차

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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