Potassium Carbonate → Desfluoro Iloperidone (Impurity)

HRID 1420164Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1420164
[NH:1]1[CH2:6][CH2:5][CH:4]([C:7]2[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=3S[N:8]=2)[CH2:3][CH2:2]1.C(=O)([O-])[O-:17].[K+].[K+].Cl[CH2:23][CH2:24][CH2:25][O:26][C:27]1[CH:32]=[CH:31][C:30]([C:33](=[O:35])[CH3:34])=[CH:29][C:28]=1[O:36][CH3:37]>[I-].[K+].C(#N)C>[O:17]1[C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=2[C:7]([CH:4]2[CH2:5][CH2:6][N:1]([CH2:23][CH2:24][CH2:25][O:26][C:27]3[CH:32]=[CH:31][C:30]([C:33](=[O:35])[CH3:34])=[CH:29][C:28]=3[O:36][CH3:37])[CH2:2][CH2:3]2)=[N:8]1

Komponenten

6

Edukt 3

HCID 11430Potassium CarbonateHCID 73142644-(3-Chloropropoxy)-3-methoxyacetophenoneHCID 133240934-(3-Benzisothiazolyl) piperidine

Produkt 1

HCID 10024423Desfluoro Iloperidone (Impurity)Ausbeute 109 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 4875Potassium IodideKatalysatorHCID 6342AcetonitrileLösungsmittel

Versuchsvorschrift

A mixture of 3-(4-piperidinyl)-1,2-benzisothiazole (3.0 g, 13.7 mmol), potassium carbonate (2.3 g, 16.5 mmol), 1-[4-(3-chloropropoxy)-3-methoxyphenyl]ethanone (4.0 g, 16.5 mmol), potassium iodide (200 mg) and acetonitrile (100 ml) was stirred at reflux under N2 for 24 hours. The cooled reaction was filtered and the cake was washed well with acetonitrile. The filtrate was concentrated to an oily residue, which was partitioned between water and ethyl acetate. The ethyl acetate extract was washed well with water, dried with MgSO4 and concentrated to yield 6.1 g of a beige oil which solidified upon standing. The product was triturated with diethyl ether and filtered to give 4.2 g of a beige solid. The compound was recrystallized from ethyl alcohol to afford 3.5 g, and another recrystallization from ethyl alcohol (utilizing decolonizing carbon) provided 2.4 g (41%) of 1-[4-[3-[4-(1,2-benzisothiazol-3-yl)-1-piperidinyl]propoxy]-3-methoxyphenyl]ethanone, m.p. 93°-95° C.

Aufarbeitung

  1. temperatureat reflux under N2 for 24 hours
  2. customThe cooled reaction
  3. filtrationwas filtered
  4. washthe cake was washed well with acetonitrile
  5. concentrationThe filtrate was concentrated to an oily residue, which
  6. customwas partitioned between water and ethyl acetate
  7. extractionThe ethyl acetate extract
  8. washwas washed well with water
  9. dry with materialdried with MgSO4
  10. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-56dfc77dc39741189dbef56891ef9591
Quelldatensatz
uspto-grants-1999_03
Patentnummer
US05889004

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