Lithium hydroxide, monohydrate → (6S,9aR)-6-(4-chlorophenyl)-3-{1-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]-(E)-methylidene}octahydroquinolizin-4-one

HRID 553992Notes

Reaction equation

HRID 553992 reaction equation
O.[OH-].[Li+].[Cl:4][C:5]1[CH:10]=[CH:9][C:8]([C@@H:11]2[CH2:20][CH2:19][CH2:18][C@H:17]3[N:12]2[C:13](=[O:29])[CH:14](P(=O)(OCC)OCC)[CH2:15][CH2:16]3)=[CH:7][CH:6]=1.[CH3:30][O:31][C:32]1[CH:33]=[C:34]([CH:37]=[CH:38][C:39]=1[N:40]1[CH:44]=[C:43]([CH3:45])[N:42]=[CH:41]1)[CH:35]=O.O.C(=O)(O)[O-].[Na+]>O1CCCC1.C(O)C.C(OCC)(=O)C>[Cl:4][C:5]1[CH:10]=[CH:9][C:8]([C@@H:11]2[CH2:20][CH2:19][CH2:18][C@H:17]3[N:12]2[C:13](=[O:29])/[C:14](=[CH:35]/[C:34]2[CH:37]=[CH:38][C:39]([N:40]4[CH:44]=[C:43]([CH3:45])[N:42]=[CH:41]4)=[C:32]([O:31][CH3:30])[CH:33]=2)/[CH2:15][CH2:16]3)=[CH:7][CH:6]=1

Participants

8

Reactant 4

HCID 168937Lithium hydroxide, monohydrateHCID 272824453-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzaldehydeHCID 86585896Sodium bicarbonate waterHCID 86612716diethyl[(6S,9aR)-6-(4-chlorophenyl)-4-oxooctahydroquinolizin-3-yl]phosphonate

Product 1

HCID 24781473(6S,9aR)-6-(4-chlorophenyl)-3-{1-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]-(E)-methylidene}octahydroquinolizin-4-one

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Iodotrimethylsilane (0.74 mL) was added to a solution of (6S,9aR)-6-(4-chlorophenyl)octahydroquinolizin-4-one (877 mg) and N,N,N′,N′-tetramethylethylenediamine (1.76 mL) in methylene chloride (25 mL) in a nitrogen atmosphere at 0° C., and the reaction solution was stirred at 0° C. for 30 minutes. Iodine (1.26 g) was added to the reaction solution at 0° C., and the reaction solution was stirred at 0° C. for one hour. A sodium thiosulfate solution and ethyl acetate were added to the reaction solution, and the organic layer was separated. The resulting organic layer was washed with brine, dried over magnesium sulfate, and then concentrated under reduced pressure to obtain (6S,9aR)-6-(4-chlorophenyl)-3-iodooctahydroquinolizin-4-one. A mixture of (6S,9aR)-6-(4-chlorophenyl)-3-iodooctahydroquinolizin-4-one with triethyl phosphite (10 mL) was stirred at 120° C. for two hours. The reaction solution was left to cool to room temperature and concentrated under reduced pressure to obtain diethyl [(6S,9aR)-6-(4-chlorophenyl)-4-oxooctahydroquinolizin-3-yl]phosphonate. Lithium hydroxide monohydrate (422 mg) was added to a mixed solution of diethyl [(6S,9aR)-6-(4-chlorophenyl)-4-oxooctahydroquinolizin-3-yl]phosphonate and 3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzaldehyde (869 mg) in tetrahydrofuran (21 mL) and ethanol (7 mL) at room temperature, and the reaction solution was stirred at room temperature for two hours. Ethyl acetate and saturated sodium bicarbonate water were added to the reaction solution, and the organic layer was separated. The resulting organic layer was washed with brine, 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 system) and then by silica gel column chromatography (elution solvent: heptane-ethyl acetate system->ethyl acetate-methanol system) to obtain 1.07 g of the title compound. The property values of the compound are as follows.

Workup

  1. customthe organic layer was separated
  2. washThe resulting organic layer was washed with brine
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (carrier: Chromatorex NH; elution solvent: heptane-ethyl acetate system)
  6. washby silica gel column chromatography (elution solvent: heptane-ethyl acetate system->ethyl acetate-methanol system)

Sources & evidence

ORD record
ord-b5c7a2dc385d41fbb44301efbf4ab7c7
Source dataset
uspto-grants-2011_11
Patent number
US08048878B2

Reaction notes

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