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

HRID 1863160Notes

Reaction equation

HRID 1863160 reaction equation
[CH3:1][N:2]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[NH:6][C:5](=O)[C:4]2=[CH:14][S:15][CH:16]=[C:3]12.O1CCCC1.[H-].[Al+3].[Li+].[H-].[H-].[H-].[OH-].[Na+]>O>[CH3:1][N:2]1[C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][C:7]=2[NH:6][CH2:5][C:4]2=[CH:14][S:15][CH:16]=[C:3]12

Participants

6

Reactant 4

HCID 8028Tetrahydrofuran2×HCID 14798Sodium HydroxideHCID 125216424,9-Dihydro-4-methyl-10H-thieno[3,4-b][1,5]benzodiazepin-10-oneHCID 21226445Aluminium lithium hydride

Product 1

HCID 203922639,10-Dihydro-4-methyl-4H-thieno[3,4-b][1,5]benzodiazepine

Reagents, catalysts & solvents 1

HCID 962WaterSolvent2×

Procedure

A mixture comprising 4 g. of 4,9-dihydro-4-methyl-10H-thieno[3,4-b][1,5]benzodiazepin-10-one [U.S. Pat. No. 3,953,430 (Example 2)] in 75 ml. of tetrahydrofuran is combined with 2 g. of lithium aluminum hydride in 50 ml. of tetrahydrofuran and refluxed under nitrogen with stirring for 10 hours. A 2 ml. portion of water is carefully added dropwise with cooling followed by 2 ml. of 15% sodium hydroxide and 6 ml. of water. The mixture is filtered and the precipitate is washed thoroughly with ether. The filtrate and washings are combined, dried over sodium sulfate, filtered and concentrated to a semi-crystalline brown oil. The product is triturated with hexane producing a tan crystalline solid. This solid is recovered, washed thoroughly with hexane and dried. This crystalline material is purified by column chromatography (alumina activity II), eluting with methylene chloride:hexane (50:50). Evaporation of the solvents yields a solid which is triturated with hexane and washed with ether, giving the desired product as pale blue crystals, mp. 125°-127° C.

Workup

  1. temperaturewith cooling
  2. filtrationThe mixture is filtered
  3. washthe precipitate is washed thoroughly with ether
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated to a semi-crystalline brown oil
  7. customThe product is triturated with hexane producing a tan crystalline solid
  8. customThis solid is recovered
  9. washwashed thoroughly with hexane
  10. customdried
  11. customThis crystalline material is purified by column chromatography (alumina activity II)
  12. washeluting with methylene chloride:hexane (50:50)
  13. customEvaporation of the solvents
  14. customyields a solid which
  15. customis triturated with hexane
  16. washwashed with ether

Sources & evidence

ORD record
ord-a800249c7ca24cfc8cdf1d5d06168fb8
Source dataset
uspto-grants-1979_09
Patent number
US04168269

Reaction notes

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