Hydrogen Bromide → alpha-Hydroxyalprazolam

HRID 2296064Notes

Reaction equation

HRID 2296064 reaction equation
C([O:8][CH2:9][C:10]1[N:14]2[C:15]3[CH:29]=[CH:28][C:27]([Cl:30])=[CH:26][C:16]=3[C:17]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)=[N:18][CH2:19][C:13]2=[N:12][N:11]=1)C1C=CC=CC=1.Br.[OH-].[Na+].O>C(O)(=O)C.C(Cl)Cl>[C:20]1([C:17]2[C:16]3[CH:26]=[C:27]([Cl:30])[CH:28]=[CH:29][C:15]=3[N:14]3[C:10]([CH2:9][OH:8])=[N:11][N:12]=[C:13]3[CH2:19][N:18]=2)[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1

Participants

7

Reactant 4

HCID 260Hydrogen BromideHCID 962WaterHCID 14798Sodium HydroxideHCID 204730831-(benzyloxymethyl)-6-phenyl-8-chloro-4H-s-triazolo[4,3-a][1,4]benzodiazepine

Product 1

HCID 162244alpha-Hydroxyalprazolam

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 6344DichloromethaneSolvent

Procedure

An amount of 25 g of 1-(benzyloxymethyl)-6-phenyl-8-chloro-4H-s-triazolo[4,3-a][1,4]benzodiazepine is dissolved in 200 ml of glacial acetic acid; to this solution are then added 170 ml of 48% aqueous hydrobromic acid. The mixture is heated for 90 minutes at 80°, and afterwards cooled to 5°; the pH-value of the mixture is adjusted with concentrated sodium hydroxide solution to 6, whilst stirring is maintained, and water and also methylene chloride are then added. The organic phase is separated, washed with saturated aqueous sodium chloride solution, dried over sodium sulphate, and concentrated by evaporation. The residue is dissolved in ethyl acetate/methanol (9:1), the solution filtered through a column of 150 g of silica gel (Merck®, particle size 0.05-0.2 mm), and the column eluted with ethyl acetate/methanol (9:1) to (7:3). The eluate is concentrated by evaporation and the residue crystallised from ethyl acetate/ether. In this manner is obtained 6-phenyl-8-chloro-4H-s-triazolo [ 4,3-a][1,4]benzodiazepine-1-methanol, M.P. 210°-211°.

Workup

  1. temperatureThe mixture is heated for 90 minutes at 80°
  2. temperatureafterwards cooled to 5°
  3. temperatureis maintained
  4. customThe organic phase is separated
  5. washwashed with saturated aqueous sodium chloride solution
  6. dry with materialdried over sodium sulphate
  7. concentrationconcentrated by evaporation
  8. dissolutionThe residue is dissolved in ethyl acetate/methanol (9:1)
  9. filtrationthe solution filtered through a column of 150 g of silica gel (Merck®, particle size 0.05-0.2 mm)
  10. washthe column eluted with ethyl acetate/methanol (9:1) to (7:3)
  11. concentrationThe eluate is concentrated by evaporation
  12. customthe residue crystallised from ethyl acetate/ether

Sources & evidence

ORD record
ord-9d0554a988444de687523a8fc23332b5
Source dataset
uspto-grants-1984_01
Patent number
US04427590

Reaction notes

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