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 16369Notes

Reaction equation

HRID 16369 reaction equation
C(OP([CH:9]1[C:18](=[O:19])[N:17]2[C@H:12]([CH2:13][CH2:14][CH2:15][C@H:16]2[C:20]2[CH:25]=[CH:24][C:23]([Cl:26])=[CH:22][CH:21]=2)[CH2:11][CH2:10]1)(=O)OCC)C.[CH3:27][O:28][C:29]1[CH:30]=[C:31]([CH:34]=[CH:35][C:36]=1[N:37]1[CH:41]=[C:40]([CH3:42])[N:39]=[CH:38]1)[CH:32]=O.O.[OH-].[Li+].C(=O)([O-])O.[Na+]>C(OCC)(=O)C.C(O)C.O1CCCC1>[Cl:26][C:23]1[CH:24]=[CH:25][C:20]([C@@H:16]2[CH2:15][CH2:14][CH2:13][C@H:12]3[N:17]2[C:18](=[O:19])/[C:9](=[CH:32]/[C:31]2[CH:34]=[CH:35][C:36]([N:37]4[CH:41]=[C:40]([CH3:42])[N:39]=[CH:38]4)=[C:29]([O:28][CH3:27])[CH:30]=2)/[CH2:10][CH2:11]3)=[CH:21][CH:22]=1

Participants

8

Reactant 4

HCID 168937Lithium hydroxide, monohydrateHCID 516892Sodium BicarbonateHCID 272824453-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzaldehydeHCID 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

In nitrogen atmosphere, trimethylsilyl iodide (0.74 mL) was added to a methylene chloride solution (25 mL) of (6S,9aR)-6-(4-chlorophenyl)-octahydroquinolizin-4-one (877 mg) and N,N,N′,N′-tetramethylethylenediamine (1.76 mL) at 0° C. The resulting reaction solution was stirred at 0° C. for 30 min, and then iodine (1.26 g) was added thereto at 0° C. The resulting reaction solution was stirred at 0° C. for 1 hr, and a sodium thiosulfate aqueous solution and ethyl acetate were added thereto. The organic layer was separated, washed with saturated saline, dried over magnesium sulfate, and concentrated under reduced pressure to give (6S,9aR)-6-(4-chlorophenyl)-3-iodooctahydroquinolizin-4-one. A mixture of the (6S,9aR)-6-(4-chlorophenyl)-3-iodooctahydroquinolizin-4-one and triethyl phosphite (10 mL) was stirred at 120° C. for 2 hr. This reaction solution was allowed to cool to room temperature and then concentrated under reduced pressure to give [(6S,9aR)-6-(4-chlorophenyl)-4-oxooctahydroquinolizin-3-yl]phosphonic acid diethyl ester. To a solution mixture of tetrahydrofuran (21 mL) and ethanol (7 mL) of the [(6S,9aR)-6-(4-chlorophenyl)-4-oxooctahydroquinolizin-3-yl]phosphonic acid diethyl ester and 3-methoxy-4-(4-methyl-1H-imidazol-1-yl)benzaldehyde (869 mg), lithium hydroxide monohydrate (422 mg) was added. The resulting reaction solution was stirred at room temperature for 2 hr, and then ethyl acetate and a saturated sodium hydrogencarbonate aqueous solution were added thereto. The organic layer was separated, washed with saturated saline, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (carrier: Chromatorex NH, eluting solvent: heptane-ethyl acetate system) and then by silica gel column chromatography (eluting solvent: heptane-ethyl acetate system and then ethyl acetate-methanol system) to give 1.07 g of the title compound. The physical property values of this compound were as follows:

Workup

  1. additionwas added
  2. customThe resulting reaction solution
  3. customThe organic layer was separated
  4. washwashed with saturated saline
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (carrier: Chromatorex NH, eluting solvent: heptane-ethyl acetate system)
  8. washby silica gel column chromatography (eluting solvent

Sources & evidence

ORD record
ord-1f28f3c362da4f2382978e056390c1fb
Source dataset
uspto-grants-2010_06
Patent number
US07737141B2

Reaction notes

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