Nitrogen → 1-[4-Chloro-6-(2,6-difluoropyridin-4-yl)-5-methylbiphenyl-2-yl]ethanone

HRID 510856

Reaktionsgleichung

Reaktionsgleichung von HRID 510856
Br[C:2]1[C:7]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=[C:6]([C:14](=[O:16])[CH3:15])[CH:5]=[C:4]([Cl:17])[C:3]=1[CH3:18].[F:19][C:20]1[CH:25]=[C:24](B(O)O)[CH:23]=[C:22]([F:29])[N:21]=1.O.N#N>O1CCOCC1.C([O-])([O-])=O.[Na+].[Na+].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:17][C:4]1[C:3]([CH3:18])=[C:2]([C:24]2[CH:23]=[C:22]([F:29])[N:21]=[C:20]([F:19])[CH:25]=2)[C:7]([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)=[C:6]([C:14](=[O:16])[CH3:15])[CH:5]=1

Komponenten

8

Edukt 4

HCID 947NitrogenHCID 962WaterHCID 27627472,6-Difluoropyridine-4-boronic acidHCID 866667871-(6-Bromo-4-chloro-5-methylbiphenyl-2-yl)ethanone

Produkt 1

HCID 866667881-[4-Chloro-6-(2,6-difluoropyridin-4-yl)-5-methylbiphenyl-2-yl]ethanoneAusbeute 30 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 10340Sodium CarbonateLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

A biphasic solution of 1-(6-bromo-4-chloro-5-methylbiphenyl-2-yl)ethanone (0.20 g, 0.62 mmol) and (2,6-difluoropyridin-4-yl)boronic acid (0.12 g, 0.74 mmol) in 1,4-dioxane (2.0 mL) and 10% Na2CO3 in water (0.98 mL, 0.93 mmol)) was bubbled with N2 to degas. After tetrakis(triphenylphosphine)palladium(0) (29 mg, 0.025 mmol) was added the mixture was bubbled with N2 for 5 min. and heated at 100° C. overnight. The mixture was cooled to room temperature and diluted with ethyl acetate. The layers were separated and the aq. layer was extracted with more ethyl acetate. The combined extracts were washed with brine, dried over Na2SO4, filtered and concentrated. The residue was purified on silica gel column, eluting with 0-30% of ethyl acetate in hexane, to give the desired product (60 mg, 30%). LCMS calculated for C20H15ClF2NO (M+H)+: m/z=358.1. found: 358.0.

Aufarbeitung

  1. customto degas
  2. customwas bubbled with N2 for 5 min.
  3. temperatureThe mixture was cooled to room temperature
  4. additiondiluted with ethyl acetate
  5. customThe layers were separated
  6. extractionthe aq. layer was extracted with more ethyl acetate
  7. washThe combined extracts were washed with brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe residue was purified on silica gel column
  12. washeluting with 0-30% of ethyl acetate in hexane

Quellen und Nachweise

ORD-Eintrag
ord-5c02a9856bba4c47b9bc7ab66ea54f41
Quelldatensatz
uspto-grants-2015_08
Patentnummer
US09096600B2

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