2-[4-[2-hydroxy-3-(propan-2-ylamino)propoxy]phenyl]acetamide

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The atenolol having low optical purity (1 mole) and p-toluic acid (1 mole) are dissolved in acetone (5 to 50 liters) with heating and the mixture is stirred at 0° to 15° C. for 5 to 24 hours. The precipitated crystals are removed by filtration, and the mother liquor is concentrated to give an optically active atenolol p-toluate with having higher optical purity, for example a salt having an optical purity of 98% ee or more from a salt having an optical purity of 91% ee in a yield of 50to 80%. In this method, when benzoic acid is used instead of p-toluic acid and chloroform is used instead of acetone, similar result is obtained. When p-t-butylbenzoic acid is used instead of p-toluic acid in the above method, the produced salt is hardly soluble in a solvent, and hence, it is necessary to use a solvent having higher solubility such as ethanol or 2-propanol instead of acetone. with heating The precipitated crystals are removed by filtration the mother liquor is concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The atenolol having low optical purity (1 mole) and p-toluic acid (1 mole) are dissolved in acetone (5 to 50 liters) with heating and the mixture is stirred at 0° to 15° C. for 5 to 24 hours. The precipitated crystals are removed by filtration, and the mother liquor is concentrated to give an optically active atenolol p-toluate with having higher optical purity, for example a salt having an optical purity of 98% ee or more from a salt having an optical purity of 91% ee in a yield of 50to 80%. In this method, when benzoic acid is used instead of p-toluic acid and chloroform is used instead of acetone, similar result is obtained. When p-t-butylbenzoic acid is used instead of p-toluic acid in the above method, the produced salt is hardly soluble in a solvent, and hence, it is necessary to use a solvent having higher solubility such as ethanol or 2-propanol instead of acetone. with heating The precipitated crystals are removed by filtration the mother liquor is concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: 20 μg (R,S)-atenolol is injected in 20 μl of the eluant acetonitrile/acetic acid (v/v, 93/7). k'R =1.18 k'S =2.34 α=2.0 RS =0.5

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: In order to prevent the reaction of produced atenolol with the optically active glycidyl ether (4) it is preferable to add the optically active glycidyl ether (4) to isopropyl amine in a solvent. The removal of excess isopropyl amine by distillation gave desired (S)-atenolol (1). Preferably, the distillation is carried out at atmospheric pressure at the initial stages and under reduced pressure at later stages, keeping the reaction mass temperature below 60° to 70° C., through out the distillation process. The crude residue may be purified, if required, by dissolving it in 1N HCl, treating this solution with activated charcoal, filtering the charcoal followed by treatment of alkali to precipitate the product. Thus, the solid product was isolated by conventional method such as filtration to get (S)-atenolol (1) of optical purity of 98% ee and above. If, necessary, the optically active (S)-atenolol (1) may be crystallized from an appropriate solvent such as water, alcohols, such as methanol, ethanol, isopropyl alcohol, butanol etc., ethers, such as diethyl ether, methyl tbutyl ether, diisopropyl ether or ketones, such as acetone, ethyl methyl ketone, methyl isobutyl ketone etc. The removal of excess isopropyl amine by distillation

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The atenolol having low optical purity (1 mole) and p-toluic acid (1 mole) are dissolved in acetone (5 to 50 liters) with heating and the mixture is stirred at 0° to 15° C. for 5 to 24 hours. The precipitated crystals are removed by filtration, and the mother liquor is concentrated to give an optically active atenolol p-toluate with having higher optical purity, for example a salt having an optical purity of 98% ee or more from a salt having an optical purity of 91% ee in a yield of 50 to 80%. In this method, when benzoic acid is used instead of p-toluic acid and chloroform is used instead of acetone, similar result is obtained. When p-t-butylbenzoic acid is used instead of p-toluic acid in the above method, the produced salt is hardly soluble in a solvent, and hence, it is necessary to use a solvent having higher solubility such as ethanol or 2-propanol instead of acetone. with heating The precipitated crystals are removed by filtration the mother liquor is concentrated

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The atenolol having low optical purity (1 mole) and p-toluic acid (1 mole) are dissolved in acetone (5 to 50 liters) with heating and the mixture is stirred at 0° to 15° C. for 5 to 24 hours. The precipitated crystals are removed by filtration, and the mother liquor is concentrated to give an optically active atenolol p-toluate with having higher optical purity, for example a salt having an optical purity of 98% ee or more from a salt having an optical purity of 91% ee in a yield of 50to 80%. In this method, when benzoic acid is used instead of p-toluic acid and chloroform is used instead of acetone, similar result is obtained. When p-t-butylbenzoic acid is used instead of p-toluic acid in the above method, the produced salt is hardly soluble in a solvent, and hence, it is necessary to use a solvent having higher solubility such as ethanol or 2-propanol instead of acetone. with heating The precipitated crystals are removed by filtration the mother liquor is concentrated