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

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Reaction Steps

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]+.

Provenance & Evidence