Benzyl Alcohol → 3,5-Bis(benzyloxy)picolinonitrile

HRID 1797987ノート

反応式

HRID 1797987 の反応式
[CH2:1]([OH:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[H-].[Na+].[H][H].Cl[C:14]1[C:15]([C:21]#[N:22])=[N:16][CH:17]=[C:18](Cl)[CH:19]=1>C1COCC1>[CH2:1]([O:8][C:14]1[C:15]([C:21]#[N:22])=[N:16][CH:17]=[C:18]([O:8][CH2:1][C:2]2[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=2)[CH:19]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

参加物

6

反応物 4

HCID 244Benzyl AlcoholHCID 24758Sodium hydrideHCID 27696993,5-Dichloro-2-cyanopyridineHCID 178418361HCID 178418361、化合物

生成物 1

HCID 534879943,5-Bis(benzyloxy)picolinonitrile収率 94%

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒

反応条件

温度
0 °C

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 (1 H, d, J=2.2 Hz), 7.25-7.37 (10 H, m), 6.78 (1 H, d, J=2.2 Hz), 5.10 (2 H, s), 5.03 (2 H, s). HPLC-MS: m/z 317 [M+H]+.

後処理

  1. temperatureto warm to room temperature
  2. temperatureThe solution is re-cooled to 0° C.
  3. customis transferred to an unfocussed Mars 5 CEM microwave reactor to 190° C.
  4. customThe reaction mixture is quenched with H2O
  5. concentrationconcentrated under reduced pressure
  6. additiondiluted with EtOAc
  7. washwashed with 2M Na2CO3, H2O and saturated aqueous NaCl
  8. dry with materialThe organic layer is dried (MgSO4)
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customto give a brown solid
  12. customThe crude solid is purified over silica (EtOAc:heptane, gradient 1:1 to 1:0)

出典と根拠

ORDレコード
ord-eff10a06929d43bcab288d09a391e52b
出典データセット
uspto-grants-2013_01
特許番号
US08343952B2

反応ノート

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