Sodium Bicarbonate → (S)-N-((S)-2-(tert-butyldimethylsilyloxy)-1-(5-fluoro-2-methoxypyridin-3-yl)ethyl)-2-methylpropane-2-sulfinamide

HRID 1426954

Reaktionsgleichung

Reaktionsgleichung von HRID 1426954
C([Li])CCC.Br[C:7]1[C:8]([O:14][CH3:15])=[N:9][CH:10]=[C:11]([F:13])[CH:12]=1.[Si:16]([O:23][CH2:24]/[CH:25]=[N:26]/[S@:27]([C:29]([CH3:32])([CH3:31])[CH3:30])=[O:28])([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:18])[CH3:17].C([O-])(O)=O.[Na+]>C1(C)C=CC=CC=1.[Cl-].[Na+].O.CCOC(C)=O>[Si:16]([O:23][CH2:24][C@@H:25]([NH:26][S@:27]([C:29]([CH3:32])([CH3:31])[CH3:30])=[O:28])[C:7]1[C:8]([O:14][CH3:15])=[N:9][CH:10]=[C:11]([F:13])[CH:12]=1)([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:18])[CH3:17]

Komponenten

8

Edukt 4

HCID 516892Sodium BicarbonateHCID 16007023(NE,S)-N-[2-[tert-butyl(dimethyl)silyl]oxyethylidene]-2-methylpropane-2-sulfinamideHCID 404270063-Bromo-5-fluoro-2-methoxypyridineHCID 178418339Butyllithium

Produkt 1

HCID 86691740(S)-N-((S)-2-(tert-butyldimethylsilyloxy)-1-(5-fluoro-2-methoxypyridin-3-yl)ethyl)-2-methylpropane-2-sulfinamideAusbeute 24 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 1140TolueneLösungsmittel3×HCID 8857Ethyl AcetateLösungsmittelHCID 57417360Sodium chloride; waterLösungsmittel

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

To a solution of n-butyl lithium (10.8 mL, 17.3 mmol, 1.6 M in hexanes) in toluene (100 mL) at −78° C. was added a solution of 3-bromo-5-fluoro-2-methoxypyridine (3.27 g, 15.9 mmol) in toluene (5 mL) dropwise, maintaining the internal temperature below −70° C. The mixture was stirred at −78° C. for 1 hour, then treated with a solution of (S,E)-N-(2-(tert-butyldimethylsilyloxy)ethylidene)-2-methylpropane-2-sulfinamide (4.0 g, 14.4 mmol) in toluene (10 mL) dropwise, maintaining the internal temperature below −65° C. After stirring at −78° C. for 3 hours the mixture was treated with brine (100 mL) and EtOAc (100 mL) and stirred at ambient temperature for 20 minutes. Saturated NaHCO3 solution (50 mL) was added and the layers were separated. The aqueous layer was extracted with EtOAc (2×50 mL) and the combined organic phases were washed with brine (50 mL), dried over Na2SO4, filtered and concentrated. The residue was purified by flash column chromatography, eluting with 10% EtOAc/hexanes to 20% EtOAc/hexanes, to afford (S)-N-((S)-2-(tert-butyldimethylsilyloxy)-1-(5-fluoro-2-methoxypyridin-3-yl)ethyl)-2-methylpropane-2-sulfinamide (1.40 g, 24% yield) mixed with a less polar impurity as a colorless oil. MS (apci) m/z=405.0 (M+H).

Aufarbeitung

  1. temperaturemaintaining the internal temperature below −70° C
  2. temperaturemaintaining the internal temperature below −65° C
  3. stirringAfter stirring at −78° C. for 3 hours the mixture
  4. stirringstirred at ambient temperature for 20 minutes
  5. customthe layers were separated
  6. extractionThe aqueous layer was extracted with EtOAc (2×50 mL)
  7. washthe combined organic phases were washed with brine (50 mL)
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe residue was purified by flash column chromatography
  12. washeluting with 10% EtOAc/hexanes to 20% EtOAc/hexanes

Quellen und Nachweise

ORD-Eintrag
ord-35a48470a202492cad888ee36adc18b9
Quelldatensatz
uspto-grants-2015_01
Patentnummer
US08933084B2

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