Реакция #417938

Уравнение реакции

epirubicin hydrochloride

diisopropyl ethyl amine

water

4-chlorobutyryl chloride

→

object product

Выход 64.0%

epirubicin

Выход 64.0%

Растворители

DMF

Условия реакции

Обработка

1. 1
   ТемператураThe mixture was cooled to 0° C.-5° C. in an ice bath
2. 2
   workup.WAITThe reaction was performed for 30 min
3. 3
   ЭкстракцияThe resulting mixture was extracted with chloroform three times (5 ml×3)
4. 4
   ПромывкаThe combined layers were washed once with saline
5. 5
   Сушкаdried over anhydrous magnesium sulfate
6. 6
   Фильтрацияfiltered
7. 7
   Другоеrotary-evaporated
8. 8
   Другоеto remove the solvent
9. 9
   ДругоеThe resultant product was purified with thin layer chromatography
10. 10
    Промывкаeluted with chloroform
11. 11
    workup.DISSOLUTIONmethanol=95:5.8 mg of the product were dissolved in 3 ml of anhydrous DMF
12. 12
    Температураcooled in an ice bath to a temperature of −5° C. to 0° C
13. 13
    workup.ADDITION0.3 mg of sodium hydride was added to the mixture
14. 14
    workup.STIRRINGThe resulting mixture was stirred for 24 hr
15. 15
    workup.ADDITION50 ml of water were added
16. 16
    ЭкстракцияThe resultant mixture was extracted three times with chloroform (5 ml×3)
17. 17
    ПромывкаThe combined layers were washed once with saturated saline
18. 18
    Сушкаdried over anhydrous magnesium sulfate
19. 19
    Фильтрацияfiltered
20. 20
    Другоеrotary-evaporated
21. 21
    Другоеto remove the solvent
22. 22
    ДругоеThe product was purified with thin layer chromatography
23. 23
    Промывкаeluted with chloroform

Методика

10 mg of epirubicin hydrochloride was dissolved in 5 ml of anhydrous DMF. The mixture was cooled to 0° C.-5° C. in an ice bath. 7 mg of diisopropyl ethyl amine was added to the mixture. The resulting mixture was stirred for 10 min. 2.4 mg of 4-chlorobutyryl chloride was added to the resulting mixture. The reaction was performed for 30 min. 100 ml of water was added to the resultant mixture in an ice bath. The resulting mixture was extracted with chloroform three times (5 ml×3). The chloroform layers were combined. The combined layers were washed once with saline, dried over anhydrous magnesium sulfate, filtered and rotary-evaporated to remove the solvent. The resultant product was purified with thin layer chromatography and eluted with chloroform:methanol=95:5.8 mg of the product were dissolved in 3 ml of anhydrous DMF. The resulting mixture was protected with argon and cooled in an ice bath to a temperature of −5° C. to 0° C. 0.3 mg of sodium hydride was added to the mixture. The resulting mixture was stirred for 24 hr. After the reaction completed, 50 ml of water were added. The resultant mixture was extracted three times with chloroform (5 ml×3). The chloroform layers were combined. The combined layers were washed once with saturated saline, dried over anhydrous magnesium sulfate, filtered and rotary-evaporated to remove the solvent. The product was purified with thin layer chromatography and eluted with chloroform:methanol=30:1 to give 6 mg of the object product. MS: 611

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