Rivastigmine → 2,3-dihydroxybutanedioic acid;[3-[(1S)-1-(dimethylamino)ethyl]phenyl] N-ethyl-N-methylcarbamate

HRID 907502Notes

Reaction equation

HRID 907502 reaction equation
[CH3:1][CH2:2][N:3]([C:5]([O:7][C:8]1[CH:9]=[CH:10][CH:11]=[C:12]([C@@H:14]([N:16]([CH3:18])[CH3:17])[CH3:15])[CH:13]=1)=[O:6])[CH3:4].[C:19]([OH:28])(=[O:27])[C@@H:20]([C@H:22]([C:24]([OH:26])=[O:25])[OH:23])[OH:21]>CC(C)=O>[CH3:1][CH2:2][N:3]([C:5]([O:7][C:8]1[CH:9]=[CH:10][CH:11]=[C:12]([C@@H:14]([N:16]([CH3:18])[CH3:17])[CH3:15])[CH:13]=1)=[O:6])[CH3:4].[CH:20]([OH:21])([C:19]([OH:28])=[O:27])[CH:22]([OH:23])[C:24]([OH:26])=[O:25]

Participants

4

Reactant 2

HCID 77991RivastigmineHCID 444305L-Tartaric acid

Product 1

HCID 99528122,3-dihydroxybutanedioic acid;[3-[(1S)-1-(dimethylamino)ethyl]phenyl] N-ethyl-N-methylcarbamateYield 85.4%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Conditions

Temperature
60 °C

Procedure

3 kg of rivastigmine freebase of Formula II in 105 lit of acetone, 1.8 kg of L-(+)-Tartaric acid was charged and heated to about 60° C. followed by stirring for about 30 minutes for complete dissolution. The resulting reaction solutions was passed through celite and wash the bed with 13.5 lit acetone to made particle free. The obtained clear solution was distilled off up to 50% of the initial volume and cooled to 30° C. 12 g of rivastigmine hydrogen tartrate was added and stirred for about 60 minutes. The reaction mixture was heated to reflux and stirred for about 60 minutes and cooled to about 30° C. and stirred for about 60 minutes for solid separation. The separated solid was filtered and washed the solid with 3 lit of acetone. Solid obtained was dried at about 60° C. for about 9 hours to afford 4.10 kg of the title compound.

Workup

  1. customThe resulting reaction solutions
  2. washwash the bed with 13.5
  3. distillationThe obtained clear solution was distilled off up to 50% of the initial volume
  4. temperaturecooled to 30° C
  5. addition12 g of rivastigmine hydrogen tartrate was added
  6. stirringstirred for about 60 minutes
  7. temperatureThe reaction mixture was heated
  8. temperatureto reflux
  9. stirringstirred for about 60 minutes
  10. temperaturecooled to about 30° C.
  11. stirringstirred for about 60 minutes for solid separation
  12. filtrationThe separated solid was filtered
  13. washwashed the solid with 3 lit of acetone
  14. customSolid obtained
  15. customwas dried at about 60° C. for about 9 hours

Sources & evidence

ORD record
ord-3284fc9a4b4f496899a3a44a6cf36b59
Source dataset
uspto-grants-2011_09
Patent number
US08013181B2

Reaction notes

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