Hydrochloric Acid → (S)-8-chloro-11,12,13,13a-tetrahydro-1-(hydroxymethy)-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepin-9-one

HRID 867537Notes

Reaction equation

HRID 867537 reaction equation
[Cl:1][C:2]1[C:7]2[C:8](=[O:24])[N:9]3[CH2:23][CH2:22][CH2:21][C@H:10]3[C:11]3[N:12]([CH:13]=[N:14][C:15]=3[C:16](OCC)=[O:17])[C:6]=2[CH:5]=[CH:4][CH:3]=1.[BH4-].[Li+].Cl.O>O1CCCC1>[Cl:1][C:2]1[C:7]2[C:8](=[O:24])[N:9]3[CH2:23][CH2:22][CH2:21][C@H:10]3[C:11]3[N:12]([CH:13]=[N:14][C:15]=3[CH2:16][OH:17])[C:6]=2[CH:5]=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 313Hydrochloric Acid2×HCID 962WaterHCID 4148881Lithium borohydrideHCID 53890667ethyl (S)-8-chloro-11,12,13,13a-tetrahydro-9-oxo-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]-benzodiazepine-1-carboxylate

Product 1

HCID 54098055(S)-8-chloro-11,12,13,13a-tetrahydro-1-(hydroxymethy)-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepin-9-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

A suspension of 81.2 g (234.8 mmol) of ethyl (S)-8-chloro-11,12,13,13a-tetrahydro-9-oxo-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepine-1-carboxylate in 450 ml of dry tetrahydrofuran is heated to about 50° and a suspension of 6.1 g (279 mmol) of lithium borohydride in 60 ml of tetrahydrofuran is added dropwise to the solution obtained. The suspension is subsequently heated to boiling under reflux for 3 hour. The mixture is cooled to room temperature and there are added dropwise thereto firstly 40 ml of 3N hydrochloric acid and then 260 ml of a solution consisting of 130 ml of conc. hydrochloric acid and 130 ml of water. The solution obtained is stirred at 40° for 15 minutes, the tetrahydrofuran is distilled off in vacuo and the aqueous residue is made alkaline with 25 percent ammonia. The precipitated material is then filtered off under suction, washed with water and dried at 80° in high vacuum. There is obtained (S)-8-chloro-11,12,13,13a-tetrahydro-1-(hydroxymethy)-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepin-9-one of melting point 303°-305° .

Workup

  1. temperatureis heated to about 50°
  2. additionis added dropwise to the solution
  3. customobtained
  4. temperatureThe suspension is subsequently heated
  5. temperatureunder reflux for 3 hour
  6. additionthere are added dropwise
  7. customThe solution obtained
  8. distillationthe tetrahydrofuran is distilled off in vacuo
  9. filtrationThe precipitated material is then filtered off under suction
  10. washwashed with water
  11. customdried at 80° in high vacuum

Sources & evidence

ORD record
ord-5b1c6cc3b06b42cd8e302d12635f97fb
Source dataset
uspto-grants-1988_10
Patent number
US04775671

Reaction notes

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