反应详情

温度

25 °C

In 1N-hydrochloric acid (44 ml)-purified water (16 ml) was dissolved crude crystal of (2S,4R)-2-[(Z)-5-carboxy-1-pentenyl]-4-(4-chlorophenylsulfonylamino)-1-(3-pyridylmethyl)pyrrolidine hydrochloride (8.0 g, 0.016 mol) followed by addition of activated carbon (0.8 g) and the mixture was stirred at 25° C. for 1 hour. Then, clarification-filtration was carried out using a 0.25μmembrane prefilter and the filtrate was washed with 1N-hydrochloric acid (4 ml)-purified water (8 ml). While the filtrate was stirred, 1N-aqueous sodium hydroxide solution was added dropwise so as to adjust the solution to pH 2.0 (pH prior to adjustment: 0.4). The mixture was stirred at 20°-25° C. for crystallization and ripening (about 1 hour, pH decreases to 1.51). Then, 1N-aqueous sodium hydroxide solution was added thereto dropwise so as to adjust the solution to pH 2.20. The solution was cooled to 5° C. and 1N aqueous sodium hydroxide solution was added thereto dropwise so as to maintain the solution at pH 2.20. The solution was cooled to 5° C. and 1N-aqueous sodium hydroxide solution was added thereto dropwise so as to maintain the solution at pH 2.20. The solution was then allowed to stand at 0°-5° C. overnight. The next morning the crystal was collected by filtration and washed with cold purified water (8 ml). The washed crystal was dried in vacuo overnight to provide pure crystal (6.77 g) of [(Z)-5-carboxy-l-pentenyl]-4-(4-chlorophenylsulfonylamino)-1-(3-pyridylmethyl)pyrrolidine hydrochloride.

1. additionfollowed by addition of activated carbon (0.8 g)
2. filtrationThen, clarification-filtration
3. washthe filtrate was washed with 1N-hydrochloric acid (4 ml)-purified water (8 ml)
4. stirringWhile the filtrate was stirred
5. addition1N-aqueous sodium hydroxide solution was added dropwise so as
6. stirringThe mixture was stirred at 20°-25° C. for crystallization
7. customabout 1 hour
8. additionThen, 1N-aqueous sodium hydroxide solution was added
9. temperatureThe solution was cooled to 5° C.
10. addition1N aqueous sodium hydroxide solution was added
11. temperaturedropwise so as to maintain the solution at pH 2.20
12. temperatureThe solution was cooled to 5° C.
13. addition1N-aqueous sodium hydroxide solution was added
14. temperaturedropwise so as to maintain the solution at pH 2.20
15. waitto stand at 0°-5° C. overnight
16. filtrationThe next morning the crystal was collected by filtration
17. washwashed
18. customwith cold purified water (8 ml)
19. customThe washed crystal was dried in vacuo overnight