反应详情

温度

54.5 °C

A mixture of noroxymorphone (62 Kg), N-ethyl-2-pyrrolidinone (186 kg), cyclopropymethyl bromide (37.8 kg) and N,N-diisopropylethylamine (36.2 kg) was heated to 52-57° C. for 24 hours and 45 min. The mixture was then diluted with a solution prepared by mixing hydrochloric acid 37% (30 kg) and water (82 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 (1975 kg). Ammonium hydroxide 4% (206 kg) was then added over three hours till pH=9-10 to precipitate the product. The solid was filtered, washed with water (2×124 kg) and dried under vacuum at 60° C. obtaining 71.3 kg of naltrexone (molar yield 89.6%). HPLC analysis (% by area): naltrexone 99.45%, noroxymorphone 0.16%, 3-cyclopropylmethylnaltrexone 0.28%

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 (1975 kg)
7. additionAmmonium hydroxide 4% (206 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 (2×124 kg)
11. customdried under vacuum at 60° C.