Butyl iodide → 3-Butylthio-4-(3-azetidinyloxy)-1,2,5-thiadiazole

HRID 264807

反応式

HRID 264807 の反応式
[H-].[Na+].C(NC([N:10]1[CH2:13][CH:12]([OH:14])[CH2:11]1)=O)(C)(C)C.Cl[C:16]1[C:20]([S:21]([CH2:24][CH3:25])(=O)=O)=[N:19][S:18][N:17]=1.I[CH2:27][CH2:28]CC>C1COCC1.O.CN(C=O)C>[CH2:24]([S:21][C:20]1[C:16]([O:14][CH:12]2[CH2:11][NH:10][CH2:13]2)=[N:17][S:18][N:19]=1)[CH2:25][CH2:27][CH3:28]

参加物

8

反応物 4

HCID 10962Butyl iodideHCID 24758Sodium hydrideHCID 105365353-Chloro-4-ethylsulfonyl-1,2,5-thiadiazoleHCID 196003721-t-Butylcarbamoyl-3-hydroxyazetidine

生成物 1

HCID 196003553-Butylthio-4-(3-azetidinyloxy)-1,2,5-thiadiazole

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 6228Dimethylformamide溶媒HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
8 °C

実験手順

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 man 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).

後処理

  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 man 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)

出典と根拠

ORDレコード
ord-19972a4e3415479eae56c0c372d7251b
出典データセット
uspto-grants-1997_07
特許番号
US05646289

関連ノート

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