Quetiapine → Quetiapine fumarate

HRID 601438Notes

Reaction equation

HRID 601438 reaction equation
[CH:1]1[CH:2]=[CH:3][C:4]2[S:15][C:14]3[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=3[N:8]=[C:7]([N:16]3[CH2:21][CH2:20][N:19]([CH2:22][CH2:23][O:24][CH2:25][CH2:26][OH:27])[CH2:18][CH2:17]3)[C:5]=2[CH:6]=1.[C:28]([OH:35])(=[O:34])/[CH:29]=[CH:30]/[C:31]([OH:33])=[O:32]>C(O)C>[CH2:18]1[N:19]([CH2:22][CH2:23][O:24][CH2:25][CH2:26][OH:27])[CH2:20][CH2:21][N:16]([C:7]2[C:5]3[C:4](=[CH:3][CH:2]=[CH:1][CH:6]=3)[S:15][C:14]3[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=3)[N:8]=2)[CH2:17]1.[CH2:18]1[N:19]([CH2:22][CH2:23][O:24][CH2:25][CH2:26][OH:27])[CH2:20][CH2:21][N:16]([C:7]2[C:5]3[C:4](=[CH:3][CH:2]=[CH:1][CH:6]=3)[S:15][C:14]3[C:9](=[CH:10][CH:11]=[CH:12][CH:13]=3)[N:8]=2)[CH2:17]1.[CH:29](/[C:28]([OH:35])=[O:34])=[CH:30]\[C:31]([OH:33])=[O:32]

Participants

4

Reactant 2

HCID 5002QuetiapineHCID 444972Fumaric Acid

Product 1

HCID 5281025Quetiapine fumarateYield 81.5%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of quetiapine (VI) (82.5 g, 215 mmol) in ethanol (660 ml) there was added fumaric acid (12.49 g, 108 mmol) and the mixture was heated under reflux for 2 hours in an inert atmosphere. A precipitate out of the solution formed shortly after starting the heating. After cooling the mixture to 0° C., it was filtered, washed with ethanol (250 ml, 0° C.) and dried at reduced pressure to give quetiapine hemifumarate (77.4 g, 81%) as a crystalline white solid.

Workup

  1. temperaturethe mixture was heated
  2. temperatureunder reflux for 2 hours in an inert atmosphere
  3. customA precipitate out of the solution formed shortly
  4. filtrationit was filtered
  5. washwashed with ethanol (250 ml, 0° C.)
  6. customdried at reduced pressure

Sources & evidence

ORD record
ord-ba171cb7c59d442ca5ca8623f5da09f1
Source dataset
uspto-grants-2011_03
Patent number
US07902355B2

Reaction notes

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