Dimethyl malonate → 2-[4-bromo-5-chloro-2-(4,4-dimethyl-3,4-dihydro-2H-quinoline-1-sulfonyl)-phenyl]-malonic acid dimethyl ester

HRID 2382709Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2382709
[C:1]([O:8][CH3:9])(=[O:7])[CH2:2][C:3]([O:5][CH3:6])=[O:4].[H-].[Na+].[Br:12][C:13]1[C:14]([Cl:35])=[CH:15][C:16](F)=[C:17]([S:19]([N:22]2[C:31]3[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=3)[C:25]([CH3:33])([CH3:32])[CH2:24][CH2:23]2)(=[O:21])=[O:20])[CH:18]=1>CN(C=O)C>[CH3:6][O:5][C:3](=[O:4])[CH:2]([C:16]1[CH:15]=[C:14]([Cl:35])[C:13]([Br:12])=[CH:18][C:17]=1[S:19]([N:22]1[C:31]2[C:26](=[CH:27][CH:28]=[CH:29][CH:30]=2)[C:25]([CH3:33])([CH3:32])[CH2:24][CH2:23]1)(=[O:21])=[O:20])[C:1]([O:8][CH3:9])=[O:7]

Komponenten

5

Edukt 3

HCID 7943Dimethyl malonateHCID 24758Sodium hydrideHCID 684692731-(5-Bromo-4-chloro-2-fluoro-benzenesulfonyl)-4,4-dimethyl-1,2,3,4-tetrahydro-quinoline

Produkt 1

HCID 684691712-[4-bromo-5-chloro-2-(4,4-dimethyl-3,4-dihydro-2H-quinoline-1-sulfonyl)-phenyl]-malonic acid dimethyl esterAusbeute 59,8 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel2×

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

To a dry DMF (10 mL) solution containing dimethyl malonate (0.79 mL, 6.9 mmol), was added NaH (276 mg, 6.9 mmol) slowly at 0° C. under N2. The slurry was stirred for 10 min, then 1-(5-bromo-4-chloro-2-fluoro-benzenesulfonyl)-4,4-dimethyl-1,2,3,4-tetrahydro-quinoline (1.0 g, 2.3 mmol) in dry DMF (5 mL) was added dropwise. The mixture was heated at 80° C. for 24 hrs, cooled to rt, carefully quenched with 1N HCl (10 mL), and extracted with ethyl acetate. The organic layer was washed with saturated aq. NaHCO3 solution and water, then was dried over MgSO4. After filtration and concentration, the residue was purified via silica gel flash column chromatography eluting with hexane/ethyl acetate (100/15) to yield 2-[4-bromo-5-chloro-2-(4,4-dimethyl-3,4-dihydro-2H-quinoline-1-sulfonyl)-phenyl]-malonic acid dimethyl ester (0.75 g). MS: 545.9 (M+H)+; tR=2.64 min (method 1)

Aufarbeitung

  1. temperaturecooled to rt
  2. customcarefully quenched with 1N HCl (10 mL)
  3. extractionextracted with ethyl acetate
  4. washThe organic layer was washed with saturated aq. NaHCO3 solution and water
  5. dry with materialwas dried over MgSO4
  6. filtrationAfter filtration and concentration
  7. customthe residue was purified via silica gel flash column chromatography
  8. washeluting with hexane/ethyl acetate (100/15)

Quellen und Nachweise

ORD-Eintrag
ord-3fd604567a6543a4a5b50510f3a14e8b
Quelldatensatz
uspto-grants-2012_09
Patentnummer
US08263588B2

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