Acetone → Quetiapine fumarate

HRID 1662949Notes

Reaction equation

HRID 1662949 reaction equation
[C:1]([OH:8])(=[O:7])/[CH:2]=[CH:3]/[C:4]([OH:6])=[O:5].CC(C)=O.O.[CH:14]1[CH:15]=[CH:16][C:17]2[S:28][C:27]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[N:21]=[C:20]([N:29]3[CH2:34][CH2:33][N:32]([CH2:35][CH2:36][O:37][CH2:38][CH2:39][OH:40])[CH2:31][CH2:30]3)[C:18]=2[CH:19]=1>C1(C)C=CC=CC=1>[CH2:31]1[N:32]([CH2:35][CH2:36][O:37][CH2:38][CH2:39][OH:40])[CH2:33][CH2:34][N:29]([C:20]2[C:18]3[C:17](=[CH:16][CH:15]=[CH:14][CH:19]=3)[S:28][C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[N:21]=2)[CH2:30]1.[CH2:31]1[N:32]([CH2:35][CH2:36][O:37][CH2:38][CH2:39][OH:40])[CH2:33][CH2:34][N:29]([C:20]2[C:18]3[C:17](=[CH:16][CH:15]=[CH:14][CH:19]=3)[S:28][C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[N:21]=2)[CH2:30]1.[CH:2](/[C:1]([OH:8])=[O:7])=[CH:3]\[C:4]([OH:6])=[O:5]

Participants

6

Reactant 4

HCID 180AcetoneHCID 962WaterHCID 5002QuetiapineHCID 444972Fumaric Acid

Product 1

HCID 5281025Quetiapine fumarateYield 150%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
2.5 °C

Procedure

0.65 g (0.006 mol) of fumaric acid is suspended in a solution of 25 ml of acetone and 5 ml of water, the solution is brought to the boil, and 25 ml of a toluene solution containing 4.5 g (0.012 mol) of pure quetiapine base is added. The solution is refluxed for approximately 5 minutes and then cooled to a temperature of 0 to 5° C., at which crystals start to precipitate. It is stirred at this temperature for 90 minutes. After being sucked off and dried, 3.8 g (0.009 mol) of quetiapine hemifumarate is obtained, i.e. 64.5% of the theory, having the HPLC purity 99.82%, and melting point 172° C.

Workup

  1. additionis added
  2. temperatureThe solution is refluxed for approximately 5 minutes
  3. customto precipitate
  4. customdried

Sources & evidence

ORD record
ord-0949414f92394d99bc69e79f4bac8ce6
Source dataset
uspto-grants-2011_10
Patent number
US08034805B2

Reaction notes

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