反应详情

温度

70 °C

Allyl bromide (56 mg; 0.463 mmol) and Et3N (45 μl; 0.327 mmol) were added to a suspension of noroxymorphone (Example 5, 100 mg; 0.348 mmol) in a mixture of NMP/H2O (10:1; 0.35 mL). The reaction vessel was purged with argon and the mixture was stirred at 70° C. for 2 h. At that time, additional Et3N (45 μl; 0.327 mmol) was added and the mixture was stirred for an additional 7.5 h at 70° C. The reaction mixture was then cooled to room temperature, diluted with dichloromethane (15 mL), and washed with saturated NaHCO3 (3×3 mL). The aqueous layer was re-extracted with dichloromethane (5 mL) and the combined organic layers were dried over MgSO4. Column chromatography of the residue (dichloromethane/methanol 4:1) afforded 96 mg (84%) of naloxone as a white solid mp: 181-182° C. (ethyl acetate), [lit. mp 173-175]xix [lit. 179.5° C. (toluene)]xx identical in all respects to the material described in the literature.xxi

1. customThe reaction vessel was purged with argon
2. stirringthe mixture was stirred for an additional 7.5 h at 70° C
3. temperatureThe reaction mixture was then cooled to room temperature
4. washwashed with saturated NaHCO3 (3×3 mL)
5. extractionThe aqueous layer was re-extracted with dichloromethane (5 mL)
6. dry with materialthe combined organic layers were dried over MgSO4