Reaction #417938

Reaction equation

epirubicin hydrochloride

diisopropyl ethyl amine

water

4-chlorobutyryl chloride

→

object product

Yield 64.0%

epirubicin

Yield 64.0%

Solvents

DMF

Conditions

Workup

1. 1
   TemperatureThe mixture was cooled to 0° C.-5° C. in an ice bath
2. 2
   workup.WAITThe reaction was performed for 30 min
3. 3
   ExtractionThe resulting mixture was extracted with chloroform three times (5 ml×3)
4. 4
   WashThe combined layers were washed once with saline
5. 5
   Dryingdried over anhydrous magnesium sulfate
6. 6
   Filtrationfiltered
7. 7
   Otherrotary-evaporated
8. 8
   Otherto remove the solvent
9. 9
   OtherThe resultant product was purified with thin layer chromatography
10. 10
    Washeluted with chloroform
11. 11
    workup.DISSOLUTIONmethanol=95:5.8 mg of the product were dissolved in 3 ml of anhydrous DMF
12. 12
    Temperaturecooled 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
    ExtractionThe resultant mixture was extracted three times with chloroform (5 ml×3)
17. 17
    WashThe combined layers were washed once with saturated saline
18. 18
    Dryingdried over anhydrous magnesium sulfate
19. 19
    Filtrationfiltered
20. 20
    Otherrotary-evaporated
21. 21
    Otherto remove the solvent
22. 22
    OtherThe product was purified with thin layer chromatography
23. 23
    Washeluted with chloroform

Procedure

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

Source