Pyridine → Rotigotine 3-Azidopropionate

HRID 389793Notes

Reaction equation

HRID 389793 reaction equation
[CH3:1][CH2:2][CH2:3][N:4]([C@@H:12]1[CH2:22][C:16]2[CH:17]=[CH:18][CH:19]=[C:20]([OH:21])[C:15]=2[CH2:14][CH2:13]1)[CH2:5][CH2:6][C:7]1[S:11][CH:10]=[CH:9][CH:8]=1.[N:23]([CH2:26][CH2:27][C:28]([OH:30])=[O:29])=[N+:24]=[N-:25].N1C=CC=CC=1>C(Cl)Cl>[CH3:1][CH2:2][CH2:3][N:4]([C@@H:12]1[CH2:22][C:16]2[CH:17]=[CH:18][CH:19]=[C:20]([OH:21])[C:15]=2[CH2:14][CH2:13]1)[CH2:5][CH2:6][C:7]1[S:11][CH:10]=[CH:9][CH:8]=1.[N:23]([CH2:26][CH2:27][C:28]([O-:30])=[O:29])=[N+:24]=[N-:25]

Participants

5

Reactant 3

HCID 1049PyridineHCID 59227Rotigotine2×HCID 155604Azidopropionic acid

Product 1

HCID 86689412Rotigotine 3-Azidopropionate

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

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.

Workup

  1. temperatureThe solution was cooled in an ice-water bath for 5 min
  2. customthe bath was removed
  3. additionTo the solution DCC was added (778 mg, 3.73 mmol, 2.4 equiv.)
  4. stirringto stir at room temperature under argon
  5. customreaction
  6. filtrationThe reaction mixture was filtered
  7. concentrationthe filtrate was concentrated to dryness on a rotary-evaporator
  8. customThe crude product was then purified by silica gel chromatography
  9. dissolutionThe crude product was dissolved in a mixed solvent of hexane-ethyl acetate (6 mL, 4:1 v/v)
  10. washThe column was eluted with hexane-ethyl acetate (4:1 v/v)
  11. customevaporated by rotary-evaporation
  12. customdried under vacuum overnight

Sources & evidence

ORD record
ord-76454497f39a4a0c87087e069ca3c4e8
Source dataset
uspto-grants-2013_02
Patent number
US08383093B1

Reaction notes

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