Hydrochloric Acid → HCID 10198204, compound

Temperature

0 °C

A mixture of anhydrous tetrahydrofuran (THF, 40 mL) and phosphorus oxychloride (36.8 g, 240 mmol) is cooled to 0° C. Into this stirred solution, a mixture of 17.23 g (200 mmol) of cyclopentanol, triethylamine (36.4 g, 360 mmol) and THF (240 mL) is added dropwise as the temperature is maintained at 0°-4° C. Some material precipitates. The cooling device is removed, and a mixture of ethanolamine (14.7 g, 240 mmol), triethylamine (36.4 g, 360 mmol) and THF (180 mL) is added to the stirred solution within 5 minutes. The temperature rises to about 55° C. and stirring is continued at this temperature for one hour. After cooling the reaction mixture to 15° C., a solution of concentrated aqueous HCl (approximate 12N, 30 mL) and water (170 mL) is added to the reaction mixture at 25°-30° C. The reaction mixture is allowed to come to ambient temperature and stirring is continued for one hour. The water layer is removed, and then the THF layer is diluted with methylene dichloride (600 mL). Sodium bicarbonate (50 g) is then added with vigorous stirring. After stirring is continued for 15 minutes, anhydrous sodium sulfate is added and stirring is resumed for a few minutes. The inorganic material is removed by filtration, and the solvent is evaporated under reduced pressure. The residue is taken up in methylene dichloride (500 mL), and the slight turbidity in the resultant solution is removed by swirling with charcoal followed by filtration of the charcoal with a glass filter. Approximately half of the volume of the methylene dichloride mixture is removed in vacuo, and acetone (200 mL) is then added to the concentrated methylene dichloride mixture. Upon cooling to 0° C. for two hours, 39.3 g (94%) of crude product precipitates. This material is dissolved in boiling 2-propanol, and then the solution is passed through a filter and cooled to room temperature. On standing overnight at room temperature, crystalline cyclopentylphosphoethanolamine is obtained and purified by chromatography. TLC: 65:25:5 CHCl3 --CH3OH--H2O; Rf =0.22

1. additionis added dropwise as the temperature
2. temperatureis maintained at 0°-4° C
3. customSome material precipitates
4. customThe cooling device is removed
5. additionis added to the stirred solution within 5 minutes
6. customrises to about 55° C.
7. temperatureAfter cooling the reaction mixture to 15° C.
8. customto come to ambient temperature
9. stirringstirring
10. waitis continued for one hour
11. customThe water layer is removed
12. additionthe THF layer is diluted with methylene dichloride (600 mL)
13. additionSodium bicarbonate (50 g) is then added with vigorous stirring
14. stirringAfter stirring
15. waitis continued for 15 minutes
16. additionanhydrous sodium sulfate is added
17. stirringstirring
18. waitis resumed for a few minutes
19. customThe inorganic material is removed by filtration
20. customthe solvent is evaporated under reduced pressure
21. customthe slight turbidity in the resultant solution is removed
22. filtrationfollowed by filtration of the charcoal with a glass
23. filtrationfilter
24. customApproximately half of the volume of the methylene dichloride mixture is removed in vacuo, and acetone (200 mL)
25. additionis then added to the concentrated methylene dichloride mixture
26. temperatureUpon cooling to 0° C. for two hours
27. custom39.3 g (94%) of crude product precipitates
28. dissolutionThis material is dissolved
29. filtrationa filter
30. temperaturecooled to room temperature
31. waitOn standing overnight at room temperature

ORD record

ord-0685a25efe6a4b9bb34969af8a02fb2c

Source dataset

uspto-grants-1998_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05804569