Methyl iodide → (E)-(6S,8R,9aR)-8-methoxy-3-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene]-6-(3,4,5-trifluorophenyl)octahydroquinolizin-4-one

HRID 553948Notes

Reaction equation

HRID 553948 reaction equation
[H-].[Na+].IC.[F:5][C:6]1[CH:7]=[C:8]([C@@H:14]2[CH2:23][C@H:22]([OH:24])[CH2:21][C@@H:20]3[N:15]2[C:16](=[O:40])/[C:17](=[CH:25]/[C:26]2[CH:31]=[CH:30][C:29]([N:32]4[CH:36]=[C:35]([CH3:37])[N:34]=[CH:33]4)=[C:28]([O:38][CH3:39])[CH:27]=2)/[CH2:18][CH2:19]3)[CH:9]=[C:10]([F:13])[C:11]=1[F:12].Br[CH2:42]CCC(N1C=CC(=O)CC1C1C=C(F)C(F)=C(F)C=1)=O>C1COCC1.C(OCC)(=O)C.O>[CH3:42][O:24][C@@H:22]1[CH2:21][C@@H:20]2[N:15]([C:16](=[O:40])/[C:17](=[CH:25]/[C:26]3[CH:31]=[CH:30][C:29]([N:32]4[CH:36]=[C:35]([CH3:37])[N:34]=[CH:33]4)=[C:28]([O:38][CH3:39])[CH:27]=3)/[CH2:18][CH2:19]2)[C@H:14]([C:8]2[CH:7]=[C:6]([F:5])[C:11]([F:12])=[C:10]([F:13])[CH:9]=2)[CH2:23]1

Participants

8

Reactant 4

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 24781747(E)-(6S*,8R*,9aR*)-6-(3,4,5-trifluorophenyl)-8-hydroxy-3-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene]octahydroquinolizin-4-oneHCID 674628841-(4-bromobutyryl)-2-(3,4,5-trifluorophenyl)-2,3-dihydro-1H-pyridin-4-one

Product 1

HCID 24781026(E)-(6S,8R,9aR)-8-methoxy-3-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene]-6-(3,4,5-trifluorophenyl)octahydroquinolizin-4-one

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

Sodium hydride (4.0 mg) and iodomethane (6.3 μL) were added to a solution of (E)-(6S,8R,9aR)-6-(3,4,5-trifluorophenyl)-8-hydroxy-3-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzylidene]octahydroquinolizin-4-one that is an optically active compound obtained in Example 71 with a retention time of 4.8 minutes (10 mg) in THF (2.0 mL) under ice-cooling, and the reaction solution was stirred at room temperature overnight. Water 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 anhydrous 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->ethyl acetate-methanol system) to obtain 3.05 mg of the title optically active compound. The property values of the optically active compound are as follows.

Workup

  1. temperaturecooling
  2. customthe organic layer was separated
  3. washThe resulting organic layer was washed with brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (carrier: Chromatorex NH; elution solvent: heptane-ethyl acetate system->ethyl acetate-methanol system)
  7. customto obtain 3.05 mg of the title optically active compound

Sources & evidence

ORD record
ord-01e51c4986054d18958c6dfd8c6025ea
Source dataset
uspto-grants-2011_11
Patent number
US08048878B2

Reaction notes

Loading…