Preparation method of oxycodone hydrochloride impurity B
A technology for oxycodone hydrochloride and impurities, which is applied in the field of preparation of oxycodone hydrochloride impurity B, and can solve the problems of difficult purification and low yield
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Embodiment 1
[0031] Example 1: 14-Hydroxin can be prepared by ketone
[0032] 30.00g Tibaine, 41.64 g of water and 26.22 g of formic acid were added to the reaction bottle, stirred, dripped with 12.30 g of oxygen water, added, heated to 48-60 ° C insulation reaction, TLC was monitored to the reaction, and the reaction liquid Water is cooled to 6 ° C and the ammonia water is added dropwise or lower than 20 ° C, and the pH is 9-10, and the aqueous phase is extracted three times (200 mL / time), combined with organic phases, wash it once with 200ml water, organic phase waterless Magnesium sulfate dried, filtered, and the filtrate was evaporated to evaporate the solvent to give 29.11 g of yellow solid.
[0033] 260 ml of dichloromethane reflux, total dissolved, 400 ml of anhydrous ethanol was added dropwise, and the mixture was stirred at room temperature for 18 hours, precipitated solid, filtered, filter cakes for 6 hours, 5.82 g of white solid, yield 86.1%.
Embodiment 2
[0034] Example 2: Preparation of Hydrohydroxone impurity B
[0035] 5.00 g 14-hydroxyl hydroxide, 150 ml of 10% aqueous potassium hydroxide aqueous solution and 150 ml of anhydrous ethanol were added to 500 ml of reaction bottles, and heated to 70-75 ° C for 70-75 ° C, and TLC was monitored to complete.
[0036] After the reaction, stirring at room temperature, 150 ml of water and 250 ml of dichloromethane, separation, and aqueous phase were added twice (250 ml / time) with dichloromethane (250 mL / time). The organic phase was dried over anhydrous magnesium sulfate, filtered, and the filtrate was evaporated to evaporase to give 5.89 g of yellow oil.
[0037] Column chromatography: 5.80 g of a silicon gel wipes, taking 5.80 g of a sample to dissolve 10 ml of dichloromethane, a wet method, and the mobile phase is eluted with methanol / dichloromethane to elute gradient, and collect the target product. The solvent was evaporated under reduced pressure to give 3.82 g of white solid, ...
Embodiment 3
[0041] Example 3 Preparation of Hydrohydroxone impurity B
[0042] 14-hydroxyl carbonate, 200 ml 10% aqueous potassium carbonate solution and 150 ml of anhydrous ethanol were added to 500 ml of reaction flask, and heated to 70-75 ° C, and TLC was monitored to complete.
[0043] After the reaction, stirring at room temperature, 150 ml of water and 250 ml of dichloromethane, separation, and aqueous phase were added twice (250 ml / time) with dichloromethane (250 mL / time). The organic phase was dried over anhydrous magnesium sulfate, filtered, and the filtrate was evaporated to evaporate the solvent to give 5.61 g of a yellow oil.
[0044] Column chromatography: 5.60 g of a silica wet method was taken at 10 ml of dichloromethane, and the mobile phase was eluted with methanol / dichloromethane to elute the gradient gradient. The solvent was evaporated under reduced pressure to give 3.66 g of white solid, yield 69.2%.
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