反応 #171323

反応方程式

acetic acid

oxycodone

Hydrochloric acid

→

oxycodone HCl

収率 96.4%

溶媒

water

反応条件

後処理

1. 1
   workup.ADDITIONwere charged into 150-mL RBF
2. 2
   その他equipped with mechanical stirrer
3. 3
   その他resulted in a thin suspension formation
4. 4
   その他followed by a precipitation)
5. 5
   workup.ADDITIONthe rest of the hydrochloric acid was added portion-wise (5 drops at once) over 40 minutes
6. 6
   workup.STIRRING(rate of stirring was increase to 250 RPM after 30 minutes)
7. 7
   workup.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. 8
   workup.ADDITIONwas added over 25 minutes
9. 9
   workup.STIRRINGStirring
10. 10
    workup.WAITcontinued for 0.5 hours
11. 11
    ろ過the precipitated product was filtered off
12. 12
    洗浄It was washed with IPA (2×40 mL) and acetone (2×40 mL)
13. 13
    その他dried
14. 14
    ろ過on filter

実験手順

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.

出典