N,N,N',N'-Tetramethylmethanediamine → Zofran

HRID 2112262Notes

Reaction equation

HRID 2112262 reaction equation
[CH3:1][N:2]1[C:14]2[CH2:13][CH2:12][CH2:11][C:10](=[O:15])[C:9]=2[C:8]2[C:3]1=[CH:4][CH:5]=[CH:6][CH:7]=2.[CH3:16][C:17]1[NH:18][CH:19]=[CH:20][N:21]=1.[CH3:22]N(CN(C)C)C.[Cl:29][Si](C)(C)C>C(#N)C.C1(C)C=CC=CC=1>[OH2:15].[OH2:15].[ClH:29].[CH3:1][N:2]1[C:14]2[CH2:13][CH2:12][CH:11]([CH2:22][N:18]3[CH:19]=[CH:20][N:21]=[C:17]3[CH3:16])[C:10](=[O:15])[C:9]=2[C:8]2[C:3]1=[CH:4][CH:5]=[CH:6][CH:7]=2

Participants

7

Reactant 4

HCID 5829N,N,N',N'-TetramethylmethanediamineHCID 6397ChlorotrimethylsilaneHCID 127492-MethylimidazoleHCID 5988759-Methyl-1,2,3,9-tetrahydro-4H-carbazol-4-one

Product 1

HCID 59774ZofranYield 53%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 6342AcetonitrileSolvent

Conditions

Temperature
10 °C

Procedure

2.0 g of 1,2,3,9-tetrahydro-9-methyl-4H-carbazol-4-one, 1.65 g of 2-methyl imidazole and 2 ml of N,N,N′,N′-tetramethyldiaminomethane were suspended in 5 ml of acetonitrile and 30 ml of toluene, and then 4 ml of chlorotrimethylsilane was slowly added thereto. The reaction mixture was stirred under reflux for 10 hours. The reaction mixture was concentrated to remove the solvent, and then 50 ml of water was added to the resulting residue. The resulting solid was filtered and dried, which was then suspended in acetone and stirred for 3 hours. The resulting solid was filtered and dried under a reduced pressure, which was then suspended in acetone, and then HCl was slowly added to thereto. The resulting suspension was stirred for 3 hours and cooled at 10° C. and below, which was then additionally stirred for 1 hour. The resulting solid was filtered and washed with acetone. The resulting solid was suspended in dichloromethane, which was then stirred under reflux for 1 hour and cooled at room temperature. The resulting solid was filtered and recrystallized with 10% aq. isopropyl alcohol to give 1.94 g of title compound (yield 53%).

Workup

  1. temperatureunder reflux for 10 hours
  2. concentrationThe reaction mixture was concentrated
  3. customto remove the solvent
  4. addition50 ml of water was added to the resulting residue
  5. filtrationThe resulting solid was filtered
  6. customdried
  7. stirringstirred for 3 hours
  8. filtrationThe resulting solid was filtered
  9. customdried under a reduced pressure, which
  10. additionHCl was slowly added to thereto
  11. stirringThe resulting suspension was stirred for 3 hours
  12. stirringbelow, which was then additionally stirred for 1 hour
  13. filtrationThe resulting solid was filtered
  14. washwashed with acetone
  15. stirringwhich was then stirred
  16. temperatureunder reflux for 1 hour
  17. temperaturecooled at room temperature
  18. filtrationThe resulting solid was filtered
  19. customrecrystallized with 10% aq. isopropyl alcohol

Sources & evidence

ORD record
ord-2f984654a007469dac0873dbf3ba9a60
Source dataset
uspto-grants-2009_04
Patent number
US07521565B2

Reaction notes

Loading…