3,9-dimethyl-3,9-diazabicyclo[3.3.1]nonan-7-one

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To N,N-bis(2,2-dimethoxyethyl)methylamine (61 g, 0.30 mol) was added distilled water (630 ml) and concentrated hydrochloric acid (101 ml, 1.21 mol) and a solution was heated to reflux for 1 hr. Subsequently, to the solution was added under ice-cooling an aqueous solution of sodium hydroxide (48.5 g sodium hydroxide, 200 ml water) (which was called "A solution"). On one hand, "A solution" was added at room temperature while stirring to an aqueous solution of disodium phosphate 12 hydrate (114.4 g) and citric acid (54.1 g) in water (709 ml) which was separately prepared. To a mixture were added acetone dicarboxylic acid (85.8 g, 0.59 mol) and methylamine hydrochloride (35.9 g, 0.53 mol). An aqueous sodium hydroxide solution was added to adjust the pH to 5 and the mixture was reacted for 15 hrs. To the reaction solution was added dropwise under ice-cooling concentrated hydrochloric acid (175 ml). The aqueous layer was washed with ethyl acetate (1000 ml×2) and sodium hydroxide (126 g) was added to the aqueous layer. The layer was extracted with chloroform (1000 ml×3), dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue (23 g) was separated by column chromatography (Florisil, ethyl acetate) to give a crude product. Recrystallization from hexane afforded the title compound (6.2 g). a solution was heated to reflux for 1 hr Subsequently, to the solution was added under ice- On one hand, "A solution" was added at room temperature was separately prepared the mixture was reacted for 15 hrs To the reaction solution was added dropwise under ice- The aqueous layer was washed with ethyl acetate (1000 ml×2) and sodium hydroxide (126 g) was added to the aqueous layer The layer was extracted with chloroform (1000 ml×3) dried over anhydrous magnesium sulfate concentrated under reduced pressure The residue (23 g) was separated by column chromatography (Florisil, ethyl acetate) to give a crude product Recrystallization from hexane

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a suspension of lithium aluminum hydride (0.95 g, 25.0 mmol) in dry THF (40 ml) was added dropwise at room temperature while stirring a solution of 7-oxo-3,9-dimethyl3,9-diazabicyclo[3.3.1)nonane (2.78 g, 16.5 mmol) in dry THF (50 ml). After stirring at room temperature for 4.5 hrs, water (1 ml), 40% aqueous sodium hydroxide solution (1 ml) and water (3 ml) were added successively to a reaction solution. Further anhydrous magnesium sulfate was added and stirred, and thereafter the reaction was filtered. The filtrate was concentrated under reduced pressure to afford the title compound (2.62 g) as an oily product. was added dropwise at room temperature stirred the reaction was filtered The filtrate was concentrated under reduced pressure

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To N,N-bis(2,2-dimethoxyethyl)methylamine (61 g, 0.30 mol) was added distilled water (630 ml) and concentrated hydrochloric acid (101 ml, 1.21 mol) and a solution was heated to reflux for 1 hr. Subsequently, to the solution was added under ice-cooling an aqueous solution of sodium hydroxide (48.5 g sodium hydroxide, 200 ml water)(which was called "A solution"). On one hand, "A solution" was added at room temperature while stirring to an aqueous solution of disodium phosphate 12 hydrate (114.4 g) and citric acid (54.1 g) in water (709 ml) which was separately prepared. To a mixture were added acetone dicarboxylic acid (85.8 g, 0.59 mol) and methylamine hydrochloride (35.9 g, 0.53 mol). An aqueous sodium hydroxide solution was added to adjust the pH to 5 and the mixture was reacted for 15 hrs. To the reaction solution was added dropwise under ice-cooling concentrated hydrochloric acid (175 ml). The aqueous layer was washed with ethyl acetate ( 1000 ml ×2) and sodium hydroxide (126 g) was added to the aqueous layer. The layer was extracted with chloroform (1000 ml ×3), dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue (23 g) was separated by column chromatography (Florisil, ethyl acetate) to give a crude product. Recrystallization from hexane afforded the title compound (6.2 g). a solution was heated to reflux for 1 hr Subsequently, to the solution was added under ice- On one hand, "A solution" was added at room temperature was separately prepared the mixture was reacted for 15 hrs To the reaction solution was added dropwise under ice- The aqueous layer was washed with ethyl acetate ( 1000 ml ×2) and sodium hydroxide (126 g) was added to the aqueous layer The layer was extracted with chloroform (1000 ml ×3) dried over anhydrous magnesium sulfate concentrated under reduced pressure The residue (23 g) was separated by column chromatography (Florisil, ethyl acetate) to give a crude product Recrystallization from hexane