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Water → 8-fluoro-4,5-dihydro-3-(hydroxymethyl)-5-methyl-6H-imidazo [1,5-a][1,4]benzodiazepin-6-one

HRID 67346
Notes
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Reaction equation

HRID 67346 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]3[CH:12]=[N:13][C:14]([C:15](OCC)=[O:16])=[C:10]3[CH2:9][N:8]([CH3:20])[C:7](=[O:21])[C:6]=2[CH:22]=1.[BH4-].[Li+].O.Cl.O>O1CCCC1>[F:1][C:2]1[CH:3]=[CH:4][C:5]2[N:11]3[CH:12]=[N:13][C:14]([CH2:15][OH:16])=[C:10]3[CH2:9][N:8]([CH3:20])[C:7](=[O:21])[C:6]=2[CH:22]=1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 4

HCID 962WaterHCID 3373FlumazenilHCID 4148881Lithium borohydrideHCID 21885828Hydrate;hydrochloride

Product 1

HCID 205153408-fluoro-4,5-dihydro-3-(hydroxymethyl)-5-methyl-6H-imidazo [1,5-a][1,4]benzodiazepin-6-one

Reagents, catalysts & solvents 1

HCID 8028
Tetrahydrofuran
Solvent
2×

Conditions

Temperature
40 °C

Procedure

15.0 g (49.5 mmol) of ethyl 8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-a][1,4]benzodiazepine-3-carboxylate are dissolved under argon in 450 ml of boiling absolute tetrahydrofuran (filtered over Alox) and added dropwise at 50° C. to a solution of 1.1 g (49.5 mmol) of lithium borohydride in 50 ml of absolute tetrahydrofuran. The mixture is stirred at 40° C. for 4 hours and at the boiling point for 2.5 hours. Subsequently, the mixture is decomposed at 40° C. with 20 ml of water and 20 ml of concentrated hydrochloric acid/water (1:1) and stirred at room temperature overnight. After removal of the tetrahydrofuran in vacuo, the residue is treated with 14 ml of concentrated ammonia. The mixture is left to crystallise in the cold and separated material is filtered off under suction and washed with water. After recrystallisation from ethanol, there is obtained 8-fluoro-4,5-dihydro-3-(hydroxymethyl)-5-methyl-6H-imidazo[ 1,5-a][1,4]benzodiazepin-6-one of melting point 221°-223° C.

Workup

  1. stirringstirred at room temperature overnight
  2. customAfter removal of the tetrahydrofuran in vacuo
  3. additionthe residue is treated with 14 ml of concentrated ammonia
  4. waitThe mixture is left
  5. customto crystallise in the cold and
  6. customseparated material
  7. filtrationis filtered off under suction
  8. washwashed with water
  9. customAfter recrystallisation from ethanol

Sources & evidence

ORD record
ord-01f48751b0e04f1c933bb4f701c04f98
Source dataset
uspto-grants-1982_08
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US04346031

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes