反应详情

700 mg (2,2 mmoles) of 3-(2-hydroxyethyl)-5-[1,2,4-triazol-1-ylmethyl]-1H-indol-2-carboxylic acid was suspended in 7 ml of dry quinoline. 14 mg of cuprous oxide was added and the stirred suspension heated, under dry nitrogen stream, to 200° C. The reaction mixture was kept at this temperature until no more CO2 was released (15-20 min.). It was left to cool to room temperature and the reaction mixture was filtered through decalite. The filtrate was concentrated by vacuum distillation of the solvent, providing a residue which was dissolved with a succinic acid solution and washed three times with 10 ml of dichloromethane. The washed aqueous phase was cooled and adjusted to pH 12 with a 40% sodium hydroxide solution and extracted three times with 20 ml of dichloromethane. The combined organic phases were dried on anhydrous sodium sulphate and evaporated to dryness. The residue was recrystallised from heptane/isopropyl acetate to give 510 mg (86%) of rizatriptan as a white solid.

1. temperaturethe stirred suspension heated, under dry nitrogen
2. customstream, to 200° C
3. custom(15-20 min.)
4. waitIt was left
5. filtrationthe reaction mixture was filtered through decalite
6. concentrationThe filtrate was concentrated by vacuum distillation of the solvent
7. customproviding a residue which
8. washwashed three times with 10 ml of dichloromethane
9. temperatureThe washed aqueous phase was cooled
10. extractionextracted three times with 20 ml of dichloromethane
11. dry with materialThe combined organic phases were dried on anhydrous sodium sulphate
12. customevaporated to dryness
13. customThe residue was recrystallised from heptane/isopropyl acetate