1,1'-Carbonyldiimidazole → (E)-(6S*,9aR*)-6-(4-cyanophenyl)-3-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene]octahydroquinolizin-4-one

HRID 553900Notes

Reaction equation

HRID 553900 reaction equation
CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O.O[CH2:24][C:25]1[CH:30]=[CH:29][C:28]([C@@H:31]2[CH2:40][CH2:39][CH2:38][C@H:37]3[N:32]2[C:33](=[O:56])/[C:34](=[CH:41]/[C:42]2[CH:47]=[CH:46][C:45]([N:48]4[CH:52]=[C:51]([CH3:53])[N:50]=[CH:49]4)=[C:44]([O:54][CH3:55])[CH:43]=2)/[CH2:35][CH2:36]3)=[CH:27][CH:26]=1.O.C(=O)(O)[O-].[Na+].Cl.NO.C([O-])(=O)C.[Na+].C(N1C=CN=C1)([N:73]1C=CN=C1)=O>C(Cl)Cl.C(O)C.C1COCC1.O.C(OCC)(=O)C>[C:24]([C:25]1[CH:30]=[CH:29][C:28]([C@@H:31]2[CH2:40][CH2:39][CH2:38][C@H:37]3[N:32]2[C:33](=[O:56])/[C:34](=[CH:41]/[C:42]2[CH:47]=[CH:46][C:45]([N:48]4[CH:52]=[C:51]([CH3:53])[N:50]=[CH:49]4)=[C:44]([O:54][CH3:55])[CH:43]=2)/[CH2:35][CH2:36]3)=[CH:27][CH:26]=1)#[N:73]

Participants

12

Reactant 6

HCID 682631,1'-CarbonyldiimidazoleHCID 159087TriacetoxyperiodinaneHCID 443297Hydroxyamine hydrochlorideHCID 517045Sodium AcetateHCID 24779886(E)-(6S*,9aR*)-6-(4-hydroxymethylphenyl)-3-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene]octahydroquinolizin-4-oneHCID 86585896Sodium bicarbonate water2×

Product 1

HCID 24780023(E)-(6S*,9aR*)-6-(4-cyanophenyl)-3-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene]octahydroquinolizin-4-oneYield 30.3%

Reagents, catalysts & solvents 5

HCID 702EthanolSolventHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent3×

Procedure

Dess-Martin periodinane (37 mg) was added to a solution of (E)-(6S*,9aR*)-6-(4-hydroxymethylphenyl)-3-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene]octahydroquinolizin-4-one (20 mg) in methylene chloride (2 mL), and the reaction solution was stirred at room temperature for 30 minutes. Saturated sodium bicarbonate water and ethyl acetate were added to the reaction solution, and the organic layer was separated. The resulting organic layer was dried over magnesium sulfate and then concentrated under reduced pressure to obtain a crude aldehyde compound. Hydroxylamine hydrochloride (9 mg) and sodium acetate (11 mg) were added to a solution of the resulting crude aldehyde compound in ethanol (3 mL), and the reaction solution was stirred at room temperature for 12 hours. Saturated sodium bicarbonate water and ethyl acetate were added to the reaction solution, and the organic layer was separated. The resulting organic layer was dried over magnesium sulfate and then concentrated under reduced pressure to obtain a crude oxime compound. To a solution of the resulting crude oxime compound in THF (5 mL), 1,1′-carbonyldiimidazole (70 mg) was added, and the reaction solution was heated to reflux for five hours. The reaction solution was left to cool to room temperature. Then, ethyl acetate and water were added to the reaction solution, and the organic layer was separated. The resulting organic layer was dried over magnesium sulfate and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (carrier: Chromatorex NH; elution solvent: heptane:ethyl acetate=1:1->ethyl acetate) to obtain 6 mg of the title compound. The property values of the compound are as follows.

Workup

  1. customthe organic layer was separated
  2. dry with materialThe resulting organic layer was dried over magnesium sulfate
  3. concentrationconcentrated under reduced pressure
  4. customto obtain a crude aldehyde compound
  5. stirringthe reaction solution was stirred at room temperature for 12 hours
  6. customthe organic layer was separated
  7. dry with materialThe resulting organic layer was dried over magnesium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customto obtain a crude oxime compound
  10. temperaturethe reaction solution was heated
  11. temperatureto reflux for five hours
  12. waitThe reaction solution was left
  13. temperatureto cool to room temperature
  14. customthe organic layer was separated
  15. dry with materialThe resulting organic layer was dried over magnesium sulfate
  16. concentrationconcentrated under reduced pressure
  17. customThe residue was purified by silica gel column chromatography (carrier: Chromatorex NH; elution solvent: heptane:ethyl acetate=1:1->ethyl acetate)

Sources & evidence

ORD record
ord-b4367328f97a44b89c40f01a8cfde382
Source dataset
uspto-grants-2011_11
Patent number
US08048878B2

Reaction notes

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