Prepare a solution of sodium methylate by dissolving 3.9 g of sodium metal in
500 ml of methanol. Add 39.0 g of 7-chloro-1,3-dihydro-5-phenyl-2H-1,4-
benzodiazepine-2-one. Evaporate the reaction mixture to a residue and
dissolve the residue in 170 ml of dimethylformamide. Add 30 g of 2,2,2-
trifluoroethyl iodide and stir at room temperature for ? hour, then heat to
60°C to 70°C for an additional 7 hours. Add 19 g of 2,2,2-trifluoroethyl iodide
and resume the heating and stirring at 60°C to 70°C for an additional 16
hours. Filter off the solids and evaporate the filtrate to a residue in vacuo.
Triturate the residue with water and extract with ethyl ether. Wash the
ethereal extract with water, dry over anhydrous sodium sulfate and evaporate the solvent to a residue.
Extract the residue with ethyl ether and filter. Concentrate the ethereal extract
to a residue. Dissolve the residue in benzene and chromatograph on 300 g of
alumina contained in a glass column 1.5 inches in diameter to give the crude
product. Elute with benzene. Crystallize this product from acetone-petroleum
ether to obtain the product.
Halazepam, 7-chloro-1,3-dihydro-5-phenyl-1(2,2,2-trifluoroethyl)-2H-1,4-benzodiazepine-2-one(Paxipam), is marketed as an anxiolytic and well absorbed. Itis active and present in plasma, but much of its activity iscaused by the major active metabolites nordazepam andoxazepam.
