反应详情

温度

8 °C

A suspension of NaH (0.24 g, 0.006 mol) in THF (30 mL) was treated with 1-t-butylcarbamoyl-3-hydroxyazetidine (1.6 g, 0.0092 mol), and the reaction stirred 1 h. After cooling to 8° C., 3-chloro-4-ethylsulfonyl-1,2,5-thiadiazole (1.96 g, 0.0092 mol) in THF (5 mL) was added, the reaction stirred 30 min, cooling removed for 30 min, and the reaction heated to 35° C. for 45 min. Heating was removed, the reaction stirred overnight, and the solvent evaporated. The residue was suspended in cold water, the mixture extracted with EtOAc, the extracts washed with brine, dried, and the solvent evaporated to give a tan liquid, (2.98 g). A DMF (30 mL) solution of the liquid was treated with freshly ground flaked Na2S-9H2O (3.3 g, 0.0138 mol). After 1 h, 1-iodobutane (2.1 mL) was added, the reaction stirred 2 h, diluted with cold water, and extracted with ether. The ether was dried, the solvent evaporated, the residue dissolved in EtOAc, and the solution treated with a stream of dry HCl for 5 min. After 1 h, the reaction was treated with icewater and the organic solvent evaporated. The aqueous solution was extracted with ether, made basic, and extracted with EtOAc. The EtOAc extracts were dried and the solvent evaporated to give a tan liquid that was purified by radial chromatography (10% EtOH-1% NH4OH--CHCl3). The HCl salt (0.41 g) crystallized from EtOAc, m.p. 138°-139° C. (Compound 51).

1. stirringthe reaction stirred 30 min
2. temperaturecooling
3. customremoved for 30 min
4. temperaturethe reaction heated to 35° C. for 45 min
5. temperatureHeating
6. customwas removed
7. stirringthe reaction stirred overnight
8. customthe solvent evaporated
9. extractionthe mixture extracted with EtOAc
10. washthe extracts washed with brine
11. customdried
12. customthe solvent evaporated
13. customto give a tan liquid, (2.98 g)
14. waitAfter 1 h
15. stirringthe reaction stirred 2 h
16. extractionextracted with ether
17. dry with materialThe ether was dried
18. customthe solvent evaporated
19. dissolutionthe residue dissolved in EtOAc
20. additionthe solution treated with a stream of dry HCl for 5 min
21. waitAfter 1 h
22. additionthe reaction was treated with icewater
23. customthe organic solvent evaporated
24. extractionThe aqueous solution was extracted with ether
25. extractionextracted with EtOAc
26. dry with materialThe EtOAc extracts were dried
27. customthe solvent evaporated
28. customto give a tan liquid that
29. customwas purified by radial chromatography (10% EtOH-1% NH4OH--CHCl3)
30. customThe HCl salt (0.41 g) crystallized from EtOAc, m.p. 138°-139° C. (Compound 51)