Iodine → (6S,9aR)-6-(4-chlorophenyl)-3-iodooctahydroquinolizin-4-one

Participants

Reaction Conditions

Reaction Steps

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.

Provenance & Evidence