Citric Acid → 3,9-Dimethyl-3,9-diazabicyclo[3.3.1]nonan-7-one

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).

1. temperaturea solution was heated
2. temperatureto reflux for 1 hr
3. additionSubsequently, to the solution was added under ice-
4. additionOn one hand, "A solution" was added at room temperature
5. customwas separately prepared
6. customthe mixture was reacted for 15 hrs
7. additionTo the reaction solution was added dropwise under ice-
8. washThe aqueous layer was washed with ethyl acetate ( 1000 ml ×2) and sodium hydroxide (126 g)
9. additionwas added to the aqueous layer
10. extractionThe layer was extracted with chloroform (1000 ml ×3)
11. dry with materialdried over anhydrous magnesium sulfate
12. concentrationconcentrated under reduced pressure
13. customThe residue (23 g) was separated by column chromatography (Florisil, ethyl acetate)
14. customto give a crude product
15. customRecrystallization from hexane

ORDレコード

ord-1f6cdb4b4f2d4fbaa2c3050a6ae21f3e

出典データセット

uspto-grants-1993_10

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US05256656