Реакция #70735

Уравнение реакции

t-BuOK

1,1-dichloro-2-propanone

cyclohexanecarbaldehyde

t-BuOK

cyanoacetamide

→

4-cyclohexyl-6-methyl-2-oxo-1,2-dihydro-3-pyridinecarbonitrile

Выход 32.0%

Растворители

THF

THF

Условия реакции

Обработка

1. 1
   ТемператураThe reaction mixture was heated
2. 2
   Температураat reflux for 2 h
3. 3
   Другоеquenched by the addition of 1.0 M HCl
4. 4
   ФильтрацияThe reaction mixture was filtered through a pad of Celite
5. 5
   Концентрированиеconcentrated in vacuo
6. 6
   workup.ADDITIONThe crude residue (10 g) was added to a solution of DMSO (150 mL)
7. 7
   workup.STIRRINGthe reaction mixture was stirred under an atmosphere of oxygen for an additional 1 h
8. 8
   ДругоеThe contents were purged with argon
9. 9
   workup.ADDITIONdiluted with 4 volumes of H2O
10. 10
    workup.ADDITION5 volumes of 4 N HCl, which were added slowly
11. 11
    ФильтрацияThe reaction mixture was filtered
12. 12
    Промывкаwashed with water
13. 13
    Другоеdried

Методика

To a stirred suspension of CrCl2 (58 g, 472.8 mmol) in THF (1500 mL) was added a THF solution (500 mL) of 1,1-dichloro-2-propanone 10 g, 78.8 mmol) and cyclohexanecarbaldehyde (8.84 g, 78.8 mmol). The reaction mixture was heated at reflux for 2 h, and then quenched by the addition of 1.0 M HCl. The reaction mixture was filtered through a pad of Celite and concentrated in vacuo. The crude residue (10 g) was added to a solution of DMSO (150 mL) containing t-BuOK (7.5 g, 65.7 mmol) and cyanoacetamide (6.1 g, 72.3 mmol) and stirred at room temperature for 30 min. Additional t-BuOK (22.5 g, 197.1 mmol) was added and the reaction mixture was stirred under an atmosphere of oxygen for an additional 1 h. The contents were purged with argon, diluted with 4 volumes of H2O, and then 5 volumes of 4 N HCl, which were added slowly. The reaction mixture was filtered, washed with water and dried to give 4-cyclohexyl-6-methyl-2-oxo-1,2-dihydro-3-pyridinecarbonitrile (4.5 g, 32%). 1H NMR (400 MHz, DMSO-d6) δ ppm 6.25 (s, 1H), 2.61-2.65 (m, 1H), 2.22 (s, 3H), 1.66-1.79 (m, 4H), 1.24-1.46 (m, 6H).

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