N,N,N',N'-Tetramethylmethanediamine → Ondansetron

HRID 2112269Notes

Reaction equation

HRID 2112269 reaction equation
[C:1](Cl)(=[O:3])[CH3:2].CN(CN(C)C)C.[CH3:12][N:13]1[C:25]2[CH2:24][CH2:23][CH2:22][C:21](=O)[C:20]=2[C:19]2[C:14]1=C[CH:16]=[CH:17][CH:18]=2.[CH3:27][C:28]1[NH:29][CH:30]=[CH:31][N:32]=1>C(#N)C.C1(C)C=CC=CC=1>[CH3:12][N:13]1[C:14]2[CH2:19][CH2:18][CH:17]([CH2:16][N:29]3[CH:30]=[CH:31][N:32]=[C:28]3[CH3:27])[C:1](=[O:3])[C:2]=2[C:20]2[C:25]1=[CH:24][CH:23]=[CH:22][CH:21]=2

Participants

7

Reactant 4

HCID 5829N,N,N',N'-TetramethylmethanediamineHCID 6367Acetyl chlorideHCID 127492-MethylimidazoleHCID 5988759-Methyl-1,2,3,9-tetrahydro-4H-carbazol-4-one

Product 1

HCID 4595OndansetronYield 81.5%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6342AcetonitrileSolvent

Procedure

To the solution of 36 ml of acetyl chloride in 50 ml of actonitrile and 750 ml of toluene, was slowly added 51 ml of N,N,N′,N′-tetramethyldiaminomethane at 0° C., which was then stirred for 10min. 50 g of 1,2,3,9-tetrahydro-9-methyl-4H-carbazol-4-one and 100 g of 2-methyl imidazole was subsequently added to the reaction mixture, which was then stirred under reflux. After completion of reaction, the reaction mixture was evaporated, and then 150 ml of water was added to the resulting residue. The resulting solid was filtered and washed, and then dried under a reduced pressure. The resulting solid was suspended in 350 ml of methanol, and then 0.7 g of active carbon was added to thereto, which was then stirred for 1 hour under reflux. The resulting mixture was filtered and washed with methanol, which was then stirred for 3 hours at room temperature. The resulting solid was filtered and dried to give 60 g of pure white title compound (yield 81.5%).

Workup

  1. customat 0° C.
  2. stirringwas then stirred
  3. temperatureunder reflux
  4. customAfter completion of reaction
  5. customthe reaction mixture was evaporated
  6. addition150 ml of water was added to the resulting residue
  7. filtrationThe resulting solid was filtered
  8. washwashed
  9. customdried under a reduced pressure
  10. addition0.7 g of active carbon was added to thereto, which
  11. stirringwas then stirred for 1 hour
  12. temperatureunder reflux
  13. filtrationThe resulting mixture was filtered
  14. washwashed with methanol, which
  15. stirringwas then stirred for 3 hours at room temperature
  16. filtrationThe resulting solid was filtered
  17. customdried

Sources & evidence

ORD record
ord-33a072ca5842464eb6f7aa85eb1ccbf8
Source dataset
uspto-grants-2009_04
Patent number
US07521565B2

Reaction notes

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