p-Toluenesulfonic acid → (E)-5-(3,4-dichlorostyryl)-2,3-dihydro-1-methyl-1H-1,4-benzodiazepin-8-ol hydrochloride

HRID 48357

Reaction equation

HRID 48357 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:26]=[CH:27][C:28]=1[Cl:29])[CH:5]=[CH:6][C:7]1=[N:8][CH2:9][CH2:10][N:11]([CH3:25])[C:12]2[CH:17]=[C:16]([O:18]C3CCCCO3)[CH:15]=[CH:14][C:13]1=2.C1(C)C=CC(S(O)(=O)=O)=CC=1>CO>[ClH:1].[Cl:1][C:2]1[CH:3]=[C:4]([CH:26]=[CH:27][C:28]=1[Cl:29])[CH:5]=[CH:6][C:7]1=[N:8][CH2:9][CH2:10][N:11]([CH3:25])[C:12]2[CH:17]=[C:16]([OH:18])[CH:15]=[CH:14][C:13]1=2

Participants

4

Reactant 2

HCID 6101p-Toluenesulfonic acid2×HCID 69893446(E)-5-(3,4-dichlorostyryl)-2,3-dihydro-8-(tetrahydro-2(RS)-pyranyloxy)-1-methyl-1H-1,4-benzodiazepine

Product 1

HCID 136386027(E)-5-(3,4-dichlorostyryl)-2,3-dihydro-1-methyl-1H-1,4-benzodiazepin-8-ol hydrochlorideYield 24.5%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of 74 mg (0.17 mmol) of (E)-5-(3,4-dichlorostyryl)-2,3-dihydro-8-(tetrahydro-2(RS)-pyranyloxy)-1-methyl-1H-1,4-benzodiazepine (prepared in EXAMPLE 114) in methanol (5 ml) was added 33 mg (0.17 mmol) p-toluenesulphonic acid and the solution stirred at room temperature for 1 hour. A further 33 mg (0.17 mmol) of p-toluenesulphonic acid was added and the solution stirred for a further 2 hours. The solvent was removed by evaporation and the residue partitioned between water and ethyl acetate. The ethyl acetate layer was washed with saturated aqueous sodium hydrogen carbonate, dried over magnesium sulphate, filtered and evaporated to dryness. The residue was chromatographed on silica gel using first dichloromethane/methanol (95:5), and then dichloromethane/methanol (9:1) for the elution. The product was dissolved in a solution of hydrogen chloride in ether and evaporated to dryness. After trituration there was obtained 8 mg of (E)-5-(3,4-dichlorostyryl)-2,3-dihydro-1-methyl-1H-1,4-benzodiazepin-8-ol hydrochloride as a dark orange solid MS: m/e 347.2 [M+H]+.

Workup

  1. stirringthe solution stirred for a further 2 hours
  2. customThe solvent was removed by evaporation
  3. customthe residue partitioned between water and ethyl acetate
  4. washThe ethyl acetate layer was washed with saturated aqueous sodium hydrogen carbonate
  5. dry with materialdried over magnesium sulphate
  6. filtrationfiltered
  7. customevaporated to dryness
  8. customThe residue was chromatographed on silica gel using first dichloromethane/methanol (95:5)
  9. washdichloromethane/methanol (9:1) for the elution
  10. dissolutionThe product was dissolved in a solution of hydrogen chloride in ether
  11. customevaporated to dryness

Sources & evidence

ORD record
ord-040b7cebbcc746f4b7fd118ae59e4f14
Source dataset
uspto-grants-2004_03
Patent number
US06703387B2

Linked notes

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