Preparation method of high-purity methylnaltrexone bromide
A technology of methylnaltrexone bromide and methylnaltrexone, which is applied in the field of preparation of methylnaltrexone bromide, can solve the problem that the quaternization reagent methyl methanesulfonate is expensive, difficult to obtain, high in cost, and difficult to obtain. Long-term problems, to achieve low cost, less impurities, good curative effect
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Embodiment 1
[0045] Embodiment 1 Contains the preparation of the mixture of morphine furan quaternary ammonium salt
[0046] Add 20ml of acetonitrile, naltrexone hydrochloride (5g, 13.2mmol), potassium carbonate (5g, 36.18mmol) and iodomethane (15g, 105.68mmol) into a 100ml single-necked bottle, install a spherical condenser, N 2 After the ball is sealed, the oil bath is heated to reflux at 60°C, and the magnetic stirring reaction is carried out for 72 hours. TLC detection (developing solvent: dichloromethane: methanol = 10:1) shows that there is no raw material, and two products are produced at Rf≈0.2 and 0.4 (Rf≈0.2 The product at the place is methylnaltrexone, and the product at Rf≈0.4 is the quaternary ammonium salt of phenolic hydroxyl methylation), stop the reaction. The reaction solution was cooled to room temperature and filtered. The filter cake was washed with an appropriate amount of acetonitrile and sucked dry. The filtrate was concentrated to dryness in a water bath at 38°C ...
Embodiment 2
[0047] Embodiment 2 Preparation of the mixture containing morphine furan quaternary ammonium salt
[0048] Add 20ml of acetone, naltrexone hydrochloride (4g, 10.55mmol), sodium carbonate (4.2g, 39.62mmol) and dimethyl sulfate (10g, 79.28mmol) into a 100ml single-necked bottle, install a spherical condenser, N 2 After the ball was sealed, the oil bath was heated at 60°C, and the reaction was stirred by magnetic force for 36 hours. TLC detection (developing solvent: dichloromethane: methanol = 10:1) showed that there was no raw material, and two products were produced at Rf ≈ 0.2 and 0.4 (Rf ≈ 0.2 The product at Rf ≈ 0.4 is methylnaltrexone, and the product at Rf ≈ 0.4 is a quaternary ammonium salt of phenolic hydroxyl methylation.), stop the reaction. The reaction solution was cooled to room temperature, filtered, and the filter cake was washed with an appropriate amount of acetonitrile and sucked dry. The filtrate was concentrated to dryness in a water bath at 38°C under red...
Embodiment 3
[0049] Embodiment 3 Preparation of the mixture containing morphine furan quaternary ammonium salt
[0050] Add 20ml of DMF, naltrexone hydrochloride (5g, 13.2mmol), triethylamine (2.8g, 27.70mmol) and dimethyl carbonate (7.5g, 83.26mmol) into a 100ml single-necked bottle, install a spherical condenser, N 2 After the ball is sealed, the oil bath is heated to reflux at 80°C, and the magnetic stirring reaction is carried out for 72 hours. TLC detection (developing solvent: dichloromethane: methanol = 10:1) shows that there is no raw material, and two products are produced at Rf≈0.2 and 0.4 (Rf≈0.2 The product at the place is methylnaltrexone, and the product at Rf≈0.4 is the quaternary ammonium salt of phenolic hydroxyl methylation.), stop the reaction. The reaction solution was cooled to room temperature and filtered. The filter cake was washed with an appropriate amount of acetonitrile and sucked dry. The filtrate was concentrated to dryness at 80°C under reduced pressure to...
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