Water → Iloperidone

HRID 1468246Notes

Reaction equation

HRID 1468246 reaction equation
Cl.[F:2][C:3]1[CH:17]=[CH:16][C:6]2[C:7]([CH:10]3[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]3)=[N:8][O:9][C:5]=2[CH:4]=1.[C:18](=O)([O-])[O-].[K+].[K+].Cl[CH2:25][CH2:26][CH2:27][O:28][C:29]1[CH:36]=[CH:35][C:32]([C:33]#N)=[CH:31][C:30]=1[O:37][CH3:38].[I-].[K+].[OH2:41]>CN(C)C=O>[CH3:18][C:33]([C:32]1[CH:35]=[CH:36][C:29]([O:28][CH2:27][CH2:26][CH2:25][N:13]2[CH2:12][CH2:11][CH:10]([C:7]3[C:6]4[CH:16]=[CH:17][C:3]([F:2])=[CH:4][C:5]=4[O:9][N:8]=3)[CH2:15][CH2:14]2)=[C:30]([O:37][CH3:38])[CH:31]=1)=[O:41]

Participants

7

Reactant 5

HCID 962WaterHCID 4875Potassium IodideHCID 11430Potassium CarbonateHCID 11334359R-56109 hydrochlorideHCID 16789618HCID 16789618, compound

Product 1

HCID 71360IloperidoneYield 78%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

6-Fluoro-3-(4-piperidinyl)-1,2benzisoxazole hydrochloride (IV) (25.5 gr., 0.1 mol.), potassium carbonate (27.0 gr., 0.2 mol.) and 80 ml. of N,N-dimethyl formamide (DMF) were charged into a clean and dry 500 ml 4 neck R.B.Flask. 4-(3′-chloropropoxy)-3-methoxybenzonitrile (V) (20.0 gr., 0.08 mol.) and potassium iodide (680 mg.) were added at about 30° C. The resultant reaction mixture was heated to about 90° C. and stirred for about 9 hrs. After completion of the reaction, the reaction mixture was cooled to about 30° C. and 400 ml. of water were charged. After stirring for 30 min., the separated solid was filtered and the solid obtained and washed with 50 ml. of water. Recrystallized from methanol and water (3:1) using decolourising carbon to afford the title compound as an off-white crystalline powder. Yield: 28.4 gr (% Yield: 78%).

Workup

  1. dry with materialdry 500 ml 4 neck R.B.Flask
  2. customThe resultant reaction mixture
  3. customAfter completion of the reaction
  4. temperaturethe reaction mixture was cooled to about 30° C.
  5. stirringAfter stirring for 30 min.
  6. filtrationthe separated solid was filtered
  7. customthe solid obtained
  8. washwashed with 50 ml
  9. customRecrystallized from methanol and water (3:1)

Sources & evidence

ORD record
ord-56f70b4576974e7facc6b72f83110d4a
Source dataset
uspto-grants-2015_04
Patent number
US09000221B2

Reaction notes

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