反应详情

温度

54.5 °C

A mixture of noroxymorphone (60 Kg, 0.209 Kmol), N-ethyl-2-pyrrolidinone (180 kg), cyclopropymethyl bromide (36.6 kg) and N,N-diisopropylethylamine (35.1 kg) was heated to 52-57° C. for 20 hours and 10 minutes. The mixture was then diluted with a solution prepared by mixing hydrochloric acid 37% (29 kg) and water (79 kg). Low boiling compounds were removed by distillation under vacuum keeping the temperature below 70° C. After cooling to 25-30° C. the mixture was further diluted with water (1910 kg). Ammonium hydroxide 4% (199 kg) was then added over three hours till pH=9-10 to precipitate the product. The solid was filtered, washed with water (2×120 kg) and dried under vacuum at 60° C. obtaining 68.5 kg of naltrexone (molar yield 93.2%). HPLC analysis (% by area): naltrexone 99.1%, noroxymorphone 0.11%, 3-cyclopropylmethylnaltrexone 0.41%

1. additionThe mixture was then diluted with a solution
2. customprepared
3. customwere removed by distillation under vacuum
4. customthe temperature below 70° C
5. temperatureAfter cooling to 25-30° C. the mixture
6. additionwas further diluted with water (1910 kg)
7. additionAmmonium hydroxide 4% (199 kg) was then added over three hours till pH=9-10
8. customto precipitate the product
9. filtrationThe solid was filtered
10. washwashed with water (2×120 kg)
11. customdried under vacuum at 60° C.