Sodium hydride → chloro(phenyl)methyl 7-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)-2-oxo-3,4-dihydroquinoline-1(2H)-carboxylate

HRID 1518670

Reaktionsgleichung

Reaktionsgleichung von HRID 1518670
[CH:1]1[CH:2]=[C:3]([N:9]2[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][CH2:17][CH2:18][O:19][C:20]3[CH:21]=[CH:22][C:23]4[CH2:30][CH2:29][C:27](=[O:28])[NH:26][C:24]=4[CH:25]=3)[CH2:11][CH2:10]2)[C:4]([Cl:8])=[C:5]([Cl:7])[CH:6]=1.[H-].[Na+].[C:33](Cl)(=[O:43])[O:34][CH:35]([Cl:42])[C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1>CC1CCCO1.C(OCC)(=O)C>[Cl:8][C:4]1[C:5]([Cl:7])=[CH:6][CH:1]=[CH:2][C:3]=1[N:9]1[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][CH2:17][CH2:18][O:19][C:20]2[CH:25]=[C:24]3[C:23]([CH2:30][CH2:29][C:27](=[O:28])[N:26]3[C:33]([O:34][CH:35]([Cl:42])[C:36]3[CH:37]=[CH:38][CH:39]=[CH:40][CH:41]=3)=[O:43])=[CH:22][CH:21]=2)[CH2:11][CH2:10]1

Komponenten

6

Edukt 3

HCID 24758Sodium hydrideHCID 60795AripiprazoleHCID 14320655Chloro(phenyl)methyl carbonochloridate

Produkt 1

HCID 66815335chloro(phenyl)methyl 7-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)-2-oxo-3,4-dihydroquinoline-1(2H)-carboxylate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 73012-MethyltetrahydrofuranLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

To a suspension of aripiprazole (1 g, 2.23 mmol) in 2-methyltetrahydrofuran (20 mL) was added NaH (178 mg, 4.46 mmol). The reaction was heated to reflux for 1.5 hours then cooled to room temperature. Chloro(phenyl)methyl carbonochloridate (1.37 g, 6.69 mmol) was then added and the reaction stirred overnight at room temperature. The reaction was cooled to 0° C., diluted with ethyl acetate (20 mL) and quenched with aqueous saturated NaHCO3 (20 mL) solution. The reaction was extracted with ethyl acetate (3×20 mL) and the combined organics washed with brine (50 mL), then dried (MgSO4) and concentrated to give chloro(phenyl)methyl 7-(4-(4-(2,3-dichlorophenyl)piperazin-1-yl)butoxy)-2-oxo-3,4-dihydroquinoline-1(2H)-carboxylate (crude yield 2.10 g) as a 1:3 mixture of product/aripiprazole. The product was taken onto the next step crude.

Aufarbeitung

  1. temperatureThe reaction was heated
  2. temperatureto reflux for 1.5 hours
  3. temperatureThe reaction was cooled to 0° C.
  4. customquenched with aqueous saturated NaHCO3 (20 mL) solution
  5. extractionThe reaction was extracted with ethyl acetate (3×20 mL)
  6. washthe combined organics washed with brine (50 mL)
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-970e7201ef9d4c48882fa491d6bdefd6
Quelldatensatz
uspto-grants-2015_07
Patentnummer
US09072788B2

Verknüpfte Notizen

Wird geladen…