تفاعل #2275694

معادلة التفاعل

3,5-dichloro-2-cyanopyridine

benzyl alcohol

sodium hydride

hydrogen

→

desired compound

المردود 94.0%

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

المردود 94.0%

المذيبات

THF

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةto warm to room temperature
2. 2
   درجة الحرارةThe solution is re-cooled to 0° C.
3. 3
   أخرىis transferred to an unfocussed Mars 5 CEM microwave reactor to 190° C.
4. 4
   أخرىThe reaction mixture is quenched with H2O
5. 5
   تركيزconcentrated under reduced pressure
6. 6
   workup.ADDITIONdiluted with EtOAc
7. 7
   غسيلwashed with 2M Na2CO3, H2O and saturated aqueous NaCl
8. 8
   تجفيفThe organic layer is dried (MgSO4)
9. 9
   ترشيحfiltered
10. 10
    تركيزconcentrated under reduced pressure
11. 11
    أخرىto give a brown solid
12. 12
    أخرىThe crude solid is purified over silica (EtOAc:heptane, gradient 1:1 to 1:0)

الإجراء التجريبي

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]+.

المصدر