Hydrochloric Acid → Oxycodone Hydrochloride

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Reaction Steps

To a 25 mL flask was charged 2.0 g (6.34 mmol, from Example 9) of low ABUK oxycodone base, 6.4 mL of ethanol and 1.3 mL of water. The mixture was stirred at RT. The batch was heated to 41-46° C., added 0.643 g (6.527 mmol, 1.03 molar equivalents) of 37% hydrochloric acid, and a solution was then resulted. The mixture was heated to 55° C. and stirred at 55° C. for 10 hours to simulate the production salt formation timeframe. The mixture was cooled to room temperature and then to 0-5° C. The mixture was stirred at 0-5° C. for 1.5 hours, filtered, and the product on the filter was rinsed with cold ethanol (2.5 mL×2) and dried. 1.899 g of oxycodone HCl (85.12% yield, as Lot 2418-123) was obtained (2.5 ppm 14-hydroxycodeinone by LC/MS, undetected 8α,14-dihydroxy-7,8-dihydrocodeinone by LC/MS and 8β,14-dihydroxy-7,8-dihydrocodeinone by LC/MS; 0.01 HPLC A % 6-oxycodol; 99.93 HPLC A % oxycodone HCl).

Provenance & Evidence