反応 #641102

反応方程式

Methylmagnesium bromide

(4S*,9aR*)-4-(4-fluorophenyl)hexahydroquinolizine-2,6-dione

ammonium chloride

ethyl acetate

methylmagnesium bromide

→

title compound

(6S*,8R*,9aR*)-6-(4-fluorophenyl)-8-hydroxy-8-methyloctahydroquinolizin-4-one

溶媒

THF

反応条件

後処理

1. 1
   温度cooling
2. 2
   workup.STIRRINGwas then stirred for 30 minutes
3. 3
   その他the organic layer was separated
4. 4
   洗浄The resulting organic layer was washed with brine
5. 5
   乾燥dried over anhydrous magnesium sulfate
6. 6
   濃縮concentrated under reduced pressure
7. 7
   その他The residue was purified by silica gel column chromatography (elution solvent: heptane-ethyl acetate system->ethyl acetate-methanol system)
8. 8
   その他to obtain

実験手順

Methylmagnesium bromide (0.96 M solution in THF, 5.98 mL) was added to a solution of (4S*,9aR*)-4-(4-fluorophenyl)hexahydroquinolizine-2,6-dione (1.0 g) in THF (15 mL) under ice-cooling, and the reaction solution was stirred for 50 minutes. Because the starting material did not disappear, methylmagnesium bromide (0.96 M solution in THF, 5.98 mL) was further added to the reaction solution, which was then stirred for 30 minutes. A saturated ammonium chloride 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 anhydrous magnesium sulfate, and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (elution solvent: heptane-ethyl acetate system->ethyl acetate-methanol system) to obtain a mixture of the starting material with the title compound. Methylmagnesium bromide (0.96 M solution in THF, 5.98 mL) was added to a solution of the resulting mixture in THF (15 mL) again under ice-cooling, and the reaction solution was stirred for one hour. A saturated ammonium chloride 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 anhydrous magnesium sulfate, and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (elution solvent: heptane-ethyl acetate system->ethyl acetate-methanol system) to obtain a mixture of the starting material with the title compound. Methylmagnesium bromide (0.96 M solution in THF, 5.98 mL) was added to a solution of the mixture obtained again in THF (15 mL) again under ice-cooling, and the reaction solution was stirred for 1.5 hours. A saturated ammonium chloride 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 anhydrous magnesium sulfate, and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (elution solvent: heptane-ethyl acetate system->ethyl acetate-methanol system) to obtain 760 mg of the title compound. The property values of the compound are as follows.

出典