Réaction #1994224

Équation de réaction

rotigotine

rotigotine

3-azidopropionic acid

pyridine

→

Rotigotine 3-Azidopropionate

Solvants

DCM

Conditions de réaction

Traitement

1. 1
   TempératureThe solution was cooled in an ice-water bath for 5 min
2. 2
   Autrethe bath was removed
3. 3
   workup.ADDITIONTo the solution DCC was added (778 mg, 3.73 mmol, 2.4 equiv.)
4. 4
   workup.STIRRINGto stir at room temperature under argon
5. 5
   Autrereaction
6. 6
   FiltrationThe reaction mixture was filtered
7. 7
   Concentrationthe filtrate was concentrated to dryness on a rotary-evaporator
8. 8
   AutreThe crude product was then purified by silica gel chromatography
9. 9
   workup.DISSOLUTIONThe crude product was dissolved in a mixed solvent of hexane-ethyl acetate (6 mL, 4:1 v/v)
10. 10
    LavageThe column was eluted with hexane-ethyl acetate (4:1 v/v)
11. 11
    Autreevaporated by rotary-evaporation
12. 12
    Autredried under vacuum overnight

Mode opératoire

In a 50 mL round bottom flask, rotigotine (500 mg, 1.56 mmol, 1 equiv.), 3-azidopropionic acid (447 mg, 3.73 mmol, 2.4 equiv.—in 5 mL DCM), and pyridine (302 μL, 3.73 mmol, 2.4 equiv.) were dissolved in 50 mL anhydrous DCM and allowed to stir under argon. The solution was cooled in an ice-water bath for 5 min, and the bath was removed. To the solution DCC was added (778 mg, 3.73 mmol, 2.4 equiv.). The solution was allowed to stir at room temperature under argon. Following overnight reaction, reverse phase HPLC analysis of the reaction mixture showed complete conversion of free rotigotine to the ester form. The reaction mixture was filtered and the filtrate was concentrated to dryness on a rotary-evaporator. The crude product was then purified by silica gel chromatography. The crude product was dissolved in a mixed solvent of hexane-ethyl acetate (6 mL, 4:1 v/v) and then loaded onto a 300 mL silica gel column (30 mm id). The column was eluted with hexane-ethyl acetate (4:1 v/v). The fractions (10 mL each) were analyzed by TLC and reversed phase HPLC. The product fractions were pooled, evaporated by rotary-evaporation, and then dried under vacuum overnight. Yield: 292 mg.

Source