Water → (5R)-5-[(E)-2-[4-(3-{[tert-butyl(dimethyl)silyl]oxy}propoxy)-3-methylphenyl]-2-(5-chloro-6-methoxypyridin-2-yl)ethenyl]pyrrolidin-2-one

HRID 70623

Reaktionsgleichung

Reaktionsgleichung von HRID 70623
C(=O)([O-])[O-].[K+].[K+].Br[CH2:8][CH2:9][CH2:10][O:11][Si:12]([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13].[Cl:19][C:20]1[CH:21]=[CH:22][C:23](/[C:28](/[C:36]2[CH:41]=[CH:40][C:39]([OH:42])=[C:38]([CH3:43])[CH:37]=2)=[CH:29]/[C@@H:30]2[NH:34][C:33](=[O:35])[CH2:32][CH2:31]2)=[N:24][C:25]=1[O:26][CH3:27].O>CN(C)C=O>[Si:12]([O:11][CH2:10][CH2:9][CH2:8][O:42][C:39]1[CH:40]=[CH:41][C:36](/[C:28](/[C:23]2[CH:22]=[CH:21][C:20]([Cl:19])=[C:25]([O:26][CH3:27])[N:24]=2)=[CH:29]\[C@@H:30]2[NH:34][C:33](=[O:35])[CH2:32][CH2:31]2)=[CH:37][C:38]=1[CH3:43])([C:15]([CH3:18])([CH3:17])[CH3:16])([CH3:14])[CH3:13]

Komponenten

6

Edukt 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 607486(3-Bromopropoxy)(tert-butyl)dimethylsilaneHCID 67398764(5R)-5-[(E)-2-(5-chloro-6-methoxypyridin-2-yl)-2-(4-hydroxy-3-methylphenyl)ethenyl]pyrrolidin-2-one

Produkt 1

HCID 67396325(5R)-5-[(E)-2-[4-(3-{[tert-butyl(dimethyl)silyl]oxy}propoxy)-3-methylphenyl]-2-(5-chloro-6-methoxypyridin-2-yl)ethenyl]pyrrolidin-2-one

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Reaktionsbedingungen

Temperatur
65 °C

Versuchsvorschrift

Potassium carbonate (470 mg) and (3-bromopropoxy)-tert-butyldimethylsilane (600 μL) were sequentially added to a solution of (5R)-5-[(E)-2-(5-chloro-6-methoxypyridin-2-yl)-2-(4-hydroxy-3-methylphenyl)ethenyl]pyrrolidin-2-one obtained in Example 4-50(2) (610 mg) in N,N-dimethylformamide (10 mL), and the mixture was stirred at room temperature for 15 hours and at 65° C. for three hours. The reaction solution was poured into water, followed by extraction with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and filtered. The solvent was then evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=6:4→2:8) to give (5R)-5-[(E)-2-[4-(3-{[tert-butyl(dimethyl)silyl]oxy}propoxy)-3-methylphenyl]-2-(5-chloro-6-methoxypyridin-2-yl)ethenyl]pyrrolidin-2-one as a colorless amorphous (879 mg, 97%).

Aufarbeitung

  1. extractionfollowed by extraction with ethyl acetate
  2. washThe organic layer was washed with brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. filtrationfiltered
  5. customThe solvent was then evaporated under reduced pressure
  6. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=6:4→2:8)

Quellen und Nachweise

ORD-Eintrag
ord-f2fd243476544d9fba6c9ca993d151fa
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08822503B2

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