反应详情

Methyltriphenylphosphonium bromide (MTPPB, 112.9 g) was suspended in 2-methyltetrahydrofuran (MTHF, 245 ml). Keeping the temperature in the range 20-25° C., KO-t-Bu (38.7 g) was charged in portions under inert atmosphere in one hour. The suspension was stirred for two hours. An anhydrous solution of naltrexone (35 g) in MTHF (144 ml) was then added over a period of one hour at 20-25° C. The suspension was maintained under stirring overnight. The mixture was then treated with a solution of glacial acetic acid (17.7 g) in MTHF. Water was then added and the pH was adjusted to 9-10. The phases were separated, the lower aqueous phase was discarded and the organic phase was washed twice with water. The organic phase was concentrated to residue under vacuum and then diluted with dichloromethane (175 ml) to give a clear solution. Concentrated aqueous hydrochloric acid (HCl 37%, 10.1 g) was added over one hour at 20-25° C. The suspension was stirred and then filtered and washed with dichloromethane and acetone. The product was dried affording 38.1 g of Nalmefene HCl.

1. additionwas charged in portions under inert atmosphere in one hour
2. temperatureThe suspension was maintained
3. stirringunder stirring overnight
4. customThe phases were separated
5. washthe organic phase was washed twice with water
6. concentrationThe organic phase was concentrated to residue under vacuum
7. additiondiluted with dichloromethane (175 ml)
8. customto give a clear solution
9. stirringThe suspension was stirred
10. filtrationfiltered
11. washwashed with dichloromethane and acetone
12. customThe product was dried