Sodium hydride → 4-((2,3-Dimethyl-4-nitrophenoxy)methyl)pyridin-2-amine

HRID 571103

Reaktionsgleichung

Reaktionsgleichung von HRID 571103
[NH2:1][C:2]1[CH:7]=[C:6]([CH2:8][OH:9])[CH:5]=[CH:4][N:3]=1.[H-].[Na+].F[C:13]1[CH:18]=[CH:17][C:16]([N+:19]([O-:21])=[O:20])=[C:15]([CH3:22])[C:14]=1[CH3:23]>CN(C=O)C.[NH4+].[Cl-].C(#N)C>[CH3:23][C:14]1[C:15]([CH3:22])=[C:16]([N+:19]([O-:21])=[O:20])[CH:17]=[CH:18][C:13]=1[O:9][CH2:8][C:6]1[CH:5]=[CH:4][N:3]=[C:2]([NH2:1])[CH:7]=1

Komponenten

7

Edukt 3

HCID 24758Sodium hydrideHCID 1515296(2-Aminopyridin-4-yl)methanolHCID 247212012,3-Dimethyl-4-fluoronitrobenzene

Produkt 1

HCID 674497664-((2,3-Dimethyl-4-nitrophenoxy)methyl)pyridin-2-amine

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 6228DimethylformamideLösungsmittel2×HCID 6342AcetonitrileLösungsmittelHCID 25517Ammonium ChlorideLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To a stirred solution of (2-aminopyridin-4-yl)methanol (1.33 g, 10.8 mmol) in DMF (10 mL) at 0° C. was added sodium hydride (60% dispersion in mineral oil, 537 mg, 13.4 mmol) and the reaction mixture maintained at 0° C. for 5 min and then warmed to RT for 1 hr. The mixture was re-cooled to 0° C., treated with a solution of 1-fluoro-2,3-dimethyl-4-nitrobenzene (2.00 g, 12.0 mmol) in DMF (5.0 mL) and after 2 min was warmed to RT. After 20 hr the reaction mixture was diluted with saturated aq. NH4Cl (50 mL) and extracted with EtOAc (2×100 mL) and then ether (100 mL). The combined organic extracts were dried and evaporated in vacuo to afford a red oil. The residue was diluted with acetonitrile (50 mL), upon which a brown precipitate formed. The precipitate was removed by filtration and the filtrate was evaporated in vacuo. This residue was purified by flash column chromatography (SiO2, 80 g, MeOH in DCM, 0-5%, gradient elution) to afford the title compound, Intermediate C3, as a yellow solid (1.19 g, 39%); Rt 1.35 (Method 2); m/z 274 (M+H)+ (ES+).

Aufarbeitung

  1. temperaturewarmed to RT for 1 hr
  2. temperatureThe mixture was re-cooled to 0° C.
  3. temperaturewas warmed to RT
  4. extractionextracted with EtOAc (2×100 mL)
  5. customThe combined organic extracts were dried
  6. customevaporated in vacuo
  7. customto afford a red oil
  8. customformed
  9. customThe precipitate was removed by filtration
  10. customthe filtrate was evaporated in vacuo
  11. customThis residue was purified by flash column chromatography (SiO2, 80 g, MeOH in DCM, 0-5%, gradient elution)

Quellen und Nachweise

ORD-Eintrag
ord-847a91f49fb940938347ef84d821417a
Quelldatensatz
uspto-grants-2015_05
Patentnummer
US09024041B2

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