Hydrochloric Acid → 9,10-Dihydro-9-methyl-4-propyl-4H-thieno[3,4-b][1,5]benzodiazepine

HRID 1863177Notes

Reaction equation

HRID 1863177 reaction equation
[CH3:1][N:2]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[N:6]([C:13](=O)[CH2:14][CH3:15])[C:5]2=[CH:17][S:18][CH:19]=[C:4]2[C:3]1=O.B.Cl>O1CCCC1>[CH3:1][N:2]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[N:6]([CH2:13][CH2:14][CH3:15])[C:5]2=[CH:17][S:18][CH:19]=[C:4]2[CH2:3]1

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 6331BoraneHCID 203922574,9-Dihydro-9-methyl-4-propionyl-10H-thieno[3,4-b][1,5]benzodiazepin-10-one

Product 1

HCID 203922729,10-Dihydro-9-methyl-4-propyl-4H-thieno[3,4-b][1,5]benzodiazepine

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A 5 g. portion of 4,9-dihydro-9-methyl-4-propionyl-10H-thieno[3,4-b][1,5]benzodiazepin-10-one is added to 200 ml. of tetrahydrofuran. To this is added 140 ml. of 1M borane, over a 15 minute period in an ice bath under nitrogen. The mixture is refluxed for 20 hours, then cooled in an ice bath and 40 ml. of 6N hydrochloric acid is added dropwise, with stirring. The tetrahydrofuran is distilled off. The reaction mixture is stirred with ice bath cooling and 31 g. of sodium hydroxide pellets are carefully added portionwise. The mixture is extracted twice with 250 ml. of benzene. Water is added to solubilize some salts. The mixture is extracted with 250 ml. of ether. The ether and benzene extracts are combined, dried over sodium sulfate, filtered and concentrated to an oil. This oil is treated with 75 ml. of ether:hexane (50:50), cooled and filtered. The filtrate is diluted with 50 ml. of hexane and cooled for a prolonged period. The solvent mixture is decanted from the insoluble material and concentrated to a solid residue. The residue is dissolved in 60 ml. of 10% methylene chloride in hexane and chromatographed on an alumina column. The column is eluted with 10% methylene chloride in hexane, discarding the first 500 ml. of eluant. Fractions 2 and 3 are collected (200 ml. each) and the eluate is changed to 20% methylene chloride in hexane. Fractions 2-7 (200 ml. each) are combined and concentrated giving the desired product as pale yellow crystals, mp. 90°-92° C.

Workup

  1. additionTo this is added 140 ml
  2. temperatureThe mixture is refluxed for 20 hours
  3. temperaturecooled in an ice bath
  4. distillationThe tetrahydrofuran is distilled off
  5. stirringThe reaction mixture is stirred with ice bath
  6. temperaturecooling
  7. additionof sodium hydroxide pellets are carefully added portionwise
  8. extractionThe mixture is extracted twice with 250 ml
  9. additionWater is added
  10. extractionThe mixture is extracted with 250 ml
  11. dry with materialdried over sodium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated to an oil
  14. additionThis oil is treated with 75 ml
  15. temperatureof ether:hexane (50:50), cooled
  16. filtrationfiltered
  17. additionThe filtrate is diluted with 50 ml
  18. temperatureof hexane and cooled for a prolonged period
  19. customThe solvent mixture is decanted from the insoluble material
  20. concentrationconcentrated to a solid residue
  21. dissolutionThe residue is dissolved in 60 ml
  22. customof 10% methylene chloride in hexane and chromatographed on an alumina column
  23. washThe column is eluted with 10% methylene chloride in hexane
  24. customFractions 2 and 3 are collected (200 ml
  25. concentrationconcentrated

Sources & evidence

ORD record
ord-9baec76a40ae491485a2945f7fa7b1e1
Source dataset
uspto-grants-1979_09
Patent number
US04168269

Reaction notes

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