Preparation method of nalbuphine free alkali
A synthesis method and compound technology, which are applied in the field of medicinal chemistry and organic synthesis, can solve the problem that the product is difficult to realize industrial production, and achieve the effect of reducing the content and improving the yield.
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Embodiment 1
[0018] In a 100 mL three-neck flask, add 1.01 g of compound II and 40 mL of absolute ethanol, stir, and control the reaction temperature to 0°C. Weigh 719 mg (1.2 eq) of sodium triacetoxyborohydride, add it to the reaction system in batches, and take samples for control every 1 h until the reaction of compound II is complete. After the reaction was finished, add 2 mL of water to quench the reaction, concentrate under reduced pressure with a rotary evaporator to remove ethanol, add saturated sodium carbonate solution to adjust the pH to about 9.0, add 10 mL of water, extract 3 times with 10 mL of ethyl acetate, collect the organic phase, and use Wash with saturated sodium chloride, add 2 g of anhydrous sodium sulfate to dry, spin dry and concentrate to obtain 0.87 g of nalbuphine free base, yield 86.0%, purity 99.01%, β-nalbuphine content=0.45%.
Embodiment 2
[0020] In a 100 mL three-necked flask, add 1.03 g of compound II and 40 mL of absolute ethanol, stir, and control the reaction temperature to 70°C. Weigh 611 mg (1.0 eq) of sodium triacetoxyborohydride, add it to the reaction system in batches, and take samples for control every 1 h until the reaction of Compound II is complete. After the reaction was finished, add 2 mL of water to quench the reaction, concentrate under reduced pressure with a rotary evaporator to remove ethanol, add saturated sodium carbonate solution to adjust the pH to about 9.0, add 10 mL of water, extract 3 times with 10 mL of ethyl acetate, collect the organic phase, and use Wash with saturated sodium chloride, add 2 g of anhydrous sodium sulfate to dry, spin dry and concentrate to obtain 0.78 g of nalbuphine free base, yield 75.70%, purity 99.12%, β-nalbuphine content=0.38%.
Embodiment 3
[0022] In a 100 mL three-neck flask, add 1.05 g of compound II and 40 mL of anhydrous methanol, stir, and control the reaction temperature to -20°C. Weigh 2.49g (4.0eq) of sodium triacetoxyborohydride, add it to the reaction system in batches, and take samples for control every 1h until the reaction of compound II is completed. After the reaction was finished, add 2 mL of water to quench the reaction, concentrate under reduced pressure with a rotary evaporator to remove methanol, add saturated sodium carbonate solution to adjust the pH to about 9.0, add 10 mL of water, extract 3 times with 10 mL of ethyl acetate, collect the organic phase, and then use Wash with saturated sodium chloride, add 2 g of anhydrous sodium sulfate to dry, spin dry and concentrate to obtain 0.76 g of nalbuphine free base with a yield of 72.4%, a purity of 99.03%, and a content of β-nalbuphine=0.52%.
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