Cyanoacetamide → 4-Cyclohexyl-6-methyl-2-oxo-1,2-dihydro-3-pyridinecarbonitrile

HRID 85532

반응식

HRID 85532 반응식
Cl[CH:2](Cl)[C:3](=O)[CH3:4].[CH:7]1([CH:13]=O)[CH2:12][CH2:11][CH2:10][CH2:9][CH2:8]1.CC([O-])(C)C.[K+].[C:21]([CH2:23][C:24]([NH2:26])=[O:25])#[N:22]>C1COCC1>[CH:7]1([C:13]2[CH:2]=[C:3]([CH3:4])[NH:26][C:24](=[O:25])[C:23]=2[C:21]#[N:22])[CH2:8][CH2:9][CH2:10][CH2:11][CH2:12]1

참가 물질

6

반응물 4

HCID 7898CyanoacetamideHCID 105671,1-DichloroacetoneHCID 16275CyclohexanecarboxaldehydeHCID 23665647Potassium tert-butoxide2회

생성물 1

HCID 152536744-Cyclohexyl-6-methyl-2-oxo-1,2-dihydro-3-pyridinecarbonitrile수율 32%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

실험 절차

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).

후처리

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 2 h
  3. customquenched by the addition of 1.0 M HCl
  4. filtrationThe reaction mixture was filtered through a pad of Celite
  5. concentrationconcentrated in vacuo
  6. additionThe crude residue (10 g) was added to a solution of DMSO (150 mL)
  7. stirringthe reaction mixture was stirred under an atmosphere of oxygen for an additional 1 h
  8. customThe contents were purged with argon
  9. additiondiluted with 4 volumes of H2O
  10. addition5 volumes of 4 N HCl, which were added slowly
  11. filtrationThe reaction mixture was filtered
  12. washwashed with water
  13. customdried

출처 및 근거

ORD 기록
ord-d493d0f7daa540a381d9b40339166e31
출처 데이터셋
uspto-grants-2014_09
특허 번호
US08846935B2

연결된 노트

불러오는 중…