5-Bromo-2-methoxypyridine → (6-Methoxypyridin-3-yl)(thiazol-5-yl)methanone

HRID 928740

Reaktionsgleichung

Reaktionsgleichung von HRID 928740
[Li]CCCC.Br[C:7]1[CH:8]=[CH:9][C:10]([O:13][CH3:14])=[N:11][CH:12]=1.CON(C)[C:18]([C:20]1[S:24][CH:23]=[N:22][CH:21]=1)=[O:19]>C1COCC1>[CH3:14][O:13][C:10]1[N:11]=[CH:12][C:7]([C:18]([C:20]2[S:24][CH:23]=[N:22][CH:21]=2)=[O:19])=[CH:8][CH:9]=1

Komponenten

5

Edukt 3

HCID 27348955-Bromo-2-methoxypyridineHCID 25307138N-Methoxy-N-methyl-1,3-thiazole-5-carboxamideHCID 178418339Butyllithium

Produkt 1

HCID 86715595(6-Methoxypyridin-3-yl)(thiazol-5-yl)methanone

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel2×

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

A n-BuLi solution (1.89 mL, 3.03 mmol, 1.6 M solution in hexane) was slowly added to a −78° C. solution of 5-bromo-2-methoxypyridine (0.392 mL, 3.03 mmol) in dry THF (10 mL). After addition, stirring was continued for an additional 40 minutes and N-methoxy-N-methylthiazole-5-carboxamide (0.600 g, 3.48 mmol, Intermediate 11: step a) dissolved in THF (10 mL) was slowly added. The mixture was stirred at −78° C. for 10 minutes then warmed to 0° C. and stirred for 1 hour. The cold solution was quenched with saturated aqueous NH4Cl and warmed to room temperature. H2O was added and layers were separated. The aqueous layer was extracted with EtOAc (3×) and the combined organic extracts washed with brine, dried (Na2SO4), filtered, evaporated in vacuo, preabsorbed onto silica gel and chromatographed (CH2Cl2/EtOAc) to provide product. The pure white solid title compound was precipitated from MeOH, filtered and dried under reduced pressure.

Aufarbeitung

  1. additionAfter addition
  2. additionwas slowly added
  3. stirringThe mixture was stirred at −78° C. for 10 minutes
  4. stirringstirred for 1 hour
  5. customThe cold solution was quenched with saturated aqueous NH4Cl
  6. temperaturewarmed to room temperature
  7. additionH2O was added
  8. customlayers were separated
  9. extractionThe aqueous layer was extracted with EtOAc (3×)
  10. washthe combined organic extracts washed with brine
  11. dry with materialdried (Na2SO4)
  12. filtrationfiltered
  13. customevaporated in vacuo
  14. custompreabsorbed onto silica gel
  15. customchromatographed (CH2Cl2/EtOAc)
  16. customto provide product
  17. customThe pure white solid title compound was precipitated from MeOH
  18. filtrationfiltered
  19. customdried under reduced pressure

Quellen und Nachweise

ORD-Eintrag
ord-9ec3a857f29f4efe82b2365c256bea0a
Quelldatensatz
uspto-grants-2016_03
Patentnummer
US09290476B2

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