Acetic Anhydride → (1R,4S)-1-acetylamino-4-(hydroxymethyl)-2-cyclopentene

Temperature

80 °C

25 g of (1R, 4 S)-1- amino-4-(hydroxymethyl)-2-cyclopentene hydrochloride were dissolved in 182 ml of acetic anhydride and, at 0° C., a solution of 18.25 g of triethylamine in 60 ml of acetic anhydride was added. The mixture was stirred at 80° C. for 3 h and then cooled to room temperature. The triethylamine hydrochloride was filtered off and washed with 120 ml of n-hexane. The filtrate was evaporated. The residue was mixed with 300 ml of toluene and stirred at room temperature in the presence of 5.2 g of active charcoal and 13 g of Celite for 20 min. After filtration and washing of the filter cake (3×40 ml of toluene), the solvent was completely evaporated off. The residue was mixed with 180 ml of methanol and 15.5 g of K2CO3 and stirred at room temperature for 10 h. The suspension was filtered and the filtrate was evaporated. The residue was suspended in 750 ml of isopropyl acetate and boiled in the presence of 0.5 g of active charcoal under reflux for 1.5 h. After the active charcoal filtration (70-80° C.), the filtrate was cooled at 0° C. overnight. The title compound was filtered, washed with 80 ml of cold isopropyl acetate and dried in vacuo. 17.2 g of product were obtained. The yield was 66%.

1. temperaturecooled to room temperature
2. filtrationThe triethylamine hydrochloride was filtered off
3. washwashed with 120 ml of n-hexane
4. customThe filtrate was evaporated
5. additionThe residue was mixed with 300 ml of toluene
6. stirringstirred at room temperature in the presence of 5.2 g of active charcoal and 13 g of Celite for 20 min
7. filtrationAfter filtration
8. washwashing of the filter cake (3×40 ml of toluene)
9. customthe solvent was completely evaporated off
10. additionThe residue was mixed with 180 ml of methanol and 15.5 g of K2CO3
11. stirringstirred at room temperature for 10 h
12. filtrationThe suspension was filtered
13. customthe filtrate was evaporated
14. temperatureunder reflux for 1.5 h
15. filtrationAfter the active charcoal filtration (70-80° C.)
16. temperaturethe filtrate was cooled at 0° C. overnight
17. filtrationThe title compound was filtered
18. washwashed with 80 ml of cold isopropyl acetate
19. customdried in vacuo

ORD record

ord-69636dc3bf6046609a0de24dd2e2a9ee

Source dataset

uspto-grants-2001_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06252112B1