Hydrochloric Acid → 8-(3-Hydroxypropyl)-8-azabicyclo[3.2.1]octan-3-one

In a nitrogen flow, 45 ml of conc. hydrochloric acid was added to a solution of 120 ml of 2,5-dimethoxytetrahydrofuran in 300 ml of water while stirring at room temperature. Twenty minutes after, the reaction solution became homogenous. Thereafter, 450 ml of water, a solution of 105 ml of 3-amino-1-propanol and 138 ml of conc. hydrochloric acid in 600 ml of water, a solution of 150 g of 1,3-diacetonedicarboxylic acid in 700 ml of water and a solution of 66 g of Na2HPO4 in 300 ml of water were successively added to the homogenous reaction solution. Furthermore, about 215 ml of 40% sodium hydroxide aqueous solution was added to the mixture. The pH of the resulting solution was then adjusted to the range of 3 to 4. After bubbling was confirmed, the mixture was stirred overnight. Then conc. hydrochloric acid was added to adjust the pH of the reaction solution to 3. The reaction solution was heated to 80° C. and stirred until bubbling of carbon dioxide gas was not observed. After completion of the reaction, the reaction solution was cooled and sodium hydroxide aqueous solution was added thereto to render alkaline. Thereafter sodium chloride was added for salting out, followed by extraction with chloroform. The chloroform layer was washed with water and then dried over anhydrous sodium sulfate. The solvent was distilled off to give 8-(3-hydroxypropyl)-8-azabicyclo[3.2.1]octan-3-one as the crude product.

1. customTwenty minutes
2. customAfter bubbling
3. stirringthe mixture was stirred overnight
4. additionThen conc. hydrochloric acid was added
5. temperatureThe reaction solution was heated to 80° C.
6. stirringstirred
7. customuntil bubbling of carbon dioxide gas
8. customAfter completion of the reaction
9. temperaturethe reaction solution was cooled
10. extractionfollowed by extraction with chloroform
11. washThe chloroform layer was washed with water
12. dry with materialdried over anhydrous sodium sulfate
13. distillationThe solvent was distilled off

ORD record

ord-8f075217bbdd48ebb679e51770137a38

Source dataset

uspto-grants-1998_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05753673