Dimethylformamide → Desfluoro Iloperidone (Impurity)

HRID 581473Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 581473
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-[4-[3-[4-(1,2-benzisoxazol-3-yl)-1-piperidinyl]propoxy]-3-methoxyphenyl]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-e7960c39597444af94d17925cb6c4168
Quelldatensatz
uspto-grants-1999_07
Patentnummer
US05919798

Notizen zur Reaktion

Wird geladen…