反应详情

Purified oxycodone base (19.22 g, 60.95 mmol, Lot S) and a mixture of water (28.83 g) and acetic acid (2.82 g, 16.19 mmol/g, 44.70 mmol) were charged into 150-mL RBF, equipped with mechanical stirrer. Stirring of the mixture at ambient temperature (230 RPM) resulted in a thin suspension formation. Hydrochloric acid (6.94 g, 10.094 mmol/g, 70.09 mmol) was added portion-wise over 45 minutes: at the beginning—about 2.30 g (over ˜4 minutes, the mixture became transparent, followed by a precipitation); the rest of the hydrochloric acid was added portion-wise (5 drops at once) over 40 minutes (rate of stirring was increase to 250 RPM after 30 minutes). The mixture was stirred for 0.5 hours at ambient temperature, 0.5 hours at ice-bath temperature, and cold IPA (0° C., 77 mL) was added over 25 minutes. Stirring continued for 0.5 hours, and the precipitated product was filtered off. It was washed with IPA (2×40 mL) and acetone (2×40 mL), dried on filter providing 21.73 g (58.76 mmol, 96.4% yield) of oxycodone HCl crystalline white solids, Lot T. Impurity profiles of materials of interest were monitored by HPLC, normalization method, as shown in Table 10.

1. additionwere charged into 150-mL RBF
2. customequipped with mechanical stirrer
3. customresulted in a thin suspension formation
4. customfollowed by a precipitation)
5. additionthe rest of the hydrochloric acid was added portion-wise (5 drops at once) over 40 minutes
6. stirring(rate of stirring was increase to 250 RPM after 30 minutes)
7. stirringThe mixture was stirred for 0.5 hours at ambient temperature, 0.5 hours at ice-bath temperature, and cold IPA (0° C., 77 mL)
8. additionwas added over 25 minutes
9. stirringStirring
10. waitcontinued for 0.5 hours
11. filtrationthe precipitated product was filtered off
12. washIt was washed with IPA (2×40 mL) and acetone (2×40 mL)
13. customdried
14. filtrationon filter