反应详情

温度

10 °C

A suspension of NaH (0.22 g, 0.009 mol) in THF (30 mL) was treated with (±)-1-t-butylcarbamoyl-3-hydroxypyrrolidine (1.73 g, 0.0092 mol), and the reaction heated to reflux for 35 min. After cooling to 10° C., chloro-4-ethylsulfonyl-1,2,5-thiadiazole (1.96 g, 0.0092 mol) in THF (5 mL) was added, cooling was removed, and the reaction heated to 35° C. for 16 h. The reaction was diluted with H2O, ether added, and the ether extract separated. The ether extract was washed with H2O, dried, and the solvent evaporated to give a tan liquid, (3.05 g). A DMF (42 mL) solution of the liquid was treated with freshly ground flaked Na2S-9H2O (3.3 g, 0.0138 mol). After 1 h, 1-iodobutane (3.42 g, 0.0186 mol) was added, and the reaction stirred at 40° C. for 16 h. The solvent was evaporated, the residue diluted with cold water, and the mixture extracted with ether. The ether was dried, the solvent evaporated, the residue dissolved in ether, and the solution treated with a stream of dry HCl for 5 min. After 66 h, the reaction was treated with ice-water and the organic solvent evaporated. The aqueous solution was extracted with ether, made basic, and extracted with ether. The ether extracts were dried and the solvent evaporated to give a tan liquid that was purified by radial chromatography (5% EtOH-0.5% NH4OH-CHCl3). The HCl salt (0.67 g) crystallized from EtOAc, m.p. 99°-100.5° C. (Compound 53).

1. temperaturethe reaction heated
2. temperatureto reflux for 35 min
3. temperaturecooling
4. customwas removed
5. temperaturethe reaction heated to 35° C. for 16 h
6. additionThe reaction was diluted with H2O, ether
7. additionadded
8. extractionthe ether extract
9. customseparated
10. extractionThe ether extract
11. washwas washed with H2O
12. customdried
13. customthe solvent evaporated
14. customto give a tan liquid, (3.05 g)
15. customThe solvent was evaporated
16. additionthe residue diluted with cold water
17. extractionthe mixture extracted with ether
18. dry with materialThe ether was dried
19. customthe solvent evaporated
20. dissolutionthe residue dissolved in ether
21. additionthe solution treated with a stream of dry HCl for 5 min
22. waitAfter 66 h
23. additionthe reaction was treated with ice-water
24. customthe organic solvent evaporated
25. extractionThe aqueous solution was extracted with ether
26. extractionextracted with ether
27. dry with materialThe ether extracts were dried
28. customthe solvent evaporated
29. customto give a tan liquid that
30. customwas purified by radial chromatography (5% EtOH-0.5% NH4OH-CHCl3)
31. customThe HCl salt (0.67 g) crystallized from EtOAc, m.p. 99°-100.5° C. (Compound 53)