Dimethylformamide → Desfluoro Iloperidone (Impurity)

HRID 1080993Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1080993
Cl.[NH:2]1[CH2:7][CH2:6][CH:5]([C:8]2[C:12]3[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=3[O:10][N:9]=2)[CH2:4][CH2:3]1.C([O-])([O-])=O.[K+].[K+].Cl[CH2:24][CH2:25][CH2:26][O:27][C:28]1[CH:33]=[CH:32][C:31]([C:34](=[O:36])[CH3:35])=[CH:30][C:29]=1[O:37][CH3:38].CN(C)C=O>O>[O:10]1[C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[C:8]([CH:5]2[CH2:4][CH2:3][N:2]([CH2:24][CH2:25][CH2:26][O:27][C:28]3[CH:33]=[CH:32][C:31]([C:34](=[O:36])[CH3:35])=[CH:30][C:29]=3[O:37][CH3:38])[CH2:7][CH2:6]2)=[N:9]1

Komponenten

6

Edukt 4

HCID 6228DimethylformamideHCID 11430Potassium CarbonateHCID 73142644-(3-Chloropropoxy)-3-methoxyacetophenoneHCID 130764373-(4-Piperidinyl)-1,2-benzisoxazole Hydrochloride

Produkt 1

HCID 10024423Desfluoro Iloperidone (Impurity)Ausbeute 47,7 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 962WaterLösungsmittel

Versuchsvorschrift

A mixture of 3-(4-piperidinyl)-1,2-benzisoxazole hydrochloride (4.8 g, 20 mmol), K2CO3 (5.2 g, 40 mmol), 1-[4-(3-chloropropoxy)-3-methoxyphenyl]ethanone (5.3 g, 22 mmol), a few crystals of KI and dimethylformamide (60 ml) was stirred at 90 C. for 16 hours. The reaction was poured into water and the aqueous mixture was extracted with ethyl acetate. The extract was washed (water), dried (MgSO4) and concentrated to afford a brown oil. The oil was chromatographed on a Waters Prep 500 utilizing silica gel columns and ethyl acetate-diethylamine (2%), as eluent. Concentration of the appropriate fractions afforded 3.9 g of product as an off-white solid. Recrystallization from absolute ethyl alcohol afforded 2.6 g (33%) of 1-[4-[3-[4-(1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-methoxypehenyl]ethanone, m.p.=102°-104° C., as colorless needles.

Aufarbeitung

  1. extractionthe aqueous mixture was extracted with ethyl acetate
  2. washThe extract was washed (water)
  3. dry with materialdried (MgSO4)
  4. concentrationconcentrated
  5. customto afford a brown oil
  6. customThe oil was chromatographed on a Waters Prep 500 utilizing silica gel columns and ethyl acetate-diethylamine (2%), as eluent

Quellen und Nachweise

ORD-Eintrag
ord-6330f69fdb2b4bb5b9780888f1d9faa6
Quelldatensatz
uspto-grants-1996_12
Patentnummer
US05583145

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