Tetrahydrofuran → HCID 22099770, compound

HRID 1863155Notes

Reaction equation

HRID 1863155 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].O1CCCC1.[CH:12]1[S:13][CH:14]=[C:15]2[C:21]=1[C:20](=O)[NH:19][C:18]1[CH:23]=[CH:24][CH:25]=[CH:26][C:17]=1[NH:16]2.[OH-].[Na+]>O>[CH:12]1[S:13][CH:14]=[C:15]2[C:21]=1[CH2:20][NH:19][C:18]1[CH:23]=[CH:24][CH:25]=[CH:26][C:17]=1[NH:16]2

Participants

6

Reactant 4

HCID 8028Tetrahydrofuran2×HCID 14798Sodium HydroxideHCID 125216414,9-dihydro-10H-thieno[3,4-b][1,5]benzodiazepin-10-oneHCID 21226445Aluminium lithium hydride

Product 1

HCID 22099770HCID 22099770, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

A reaction mixture comprising 3.8 g. of lithium aluminum hydride in 100 ml. of dry tetrahydrofuran, 5 g. of 4,9-dihydro-10H-thieno[3,4-b][1,5]benzodiazepin-10-one [U.S. Pat. No. 3,953,430 (Example 25)] and 125 ml. of dry tetrahydrofuran is heated, with stirring under reflux for 18 hours. The reaction mixture is cooled and 4 ml. of water is carefully added dropwise with stirring and ice bath cooling. Following this, 4 ml. of 15% sodium hydroxide and 12 ml. of water are added. The mixture is filtered and the precipitate is washed thoroughly with tetrahydrofuran and ether. The combined organic phases are dried over sodium sulfate filtered and the filtrate is concentrated to dryness. The dark brownish-green crystals are triturated in hexane, filtered, washed with hexane and dried. The product is heated to boiling in 50 ml. of chloroform, filtered and the filtrate is combined with 50 ml. of hexane and cooled in a chill room. The crystals are recovered by filtration, washed with hexane and dried. Recrystallization from chloroform-hexane is repeated. A 200 mg. portion of these crystals is recrystallized by dissolving in 10 ml. of chloroform with warming, treating with activated charcoal, filtering through diatomaceous earth and adding 20 ml. of hexane to the filtrate. These crystals are collected, washed with hexane, and dried giving the desired final product, mp. 167°-169° C.

Workup

  1. temperatureunder reflux for 18 hours
  2. temperatureThe reaction mixture is cooled
  3. stirringwith stirring
  4. temperatureice bath cooling
  5. filtrationThe mixture is filtered
  6. washthe precipitate is washed thoroughly with tetrahydrofuran and ether
  7. dry with materialThe combined organic phases are dried over sodium sulfate
  8. filtrationfiltered
  9. concentrationthe filtrate is concentrated to dryness
  10. customThe dark brownish-green crystals are triturated in hexane
  11. filtrationfiltered
  12. washwashed with hexane
  13. customdried
  14. temperatureThe product is heated
  15. filtrationof chloroform, filtered
  16. temperatureof hexane and cooled in a chill room
  17. filtrationThe crystals are recovered by filtration
  18. washwashed with hexane
  19. customdried
  20. customRecrystallization from chloroform-hexane
  21. customportion of these crystals is recrystallized
  22. dissolutionby dissolving in 10 ml
  23. temperatureof chloroform with warming
  24. additiontreating with activated charcoal
  25. filtrationfiltering through diatomaceous earth
  26. additionadding 20 ml
  27. customThese crystals are collected
  28. washwashed with hexane
  29. customdried

Sources & evidence

ORD record
ord-875f4b3de4f14571a15eb0ab9f625a58
Source dataset
uspto-grants-1979_09
Patent number
US04168269

Reaction notes

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