2',5'-Dimethoxyacetophenone → 2-(3,4-Difluoro-5-methoxyphenyl)-1-(2,5-dimethoxyphenyl)ethanone

HRID 2368922Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2368922
C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.CC([O-])(C)C.[Na+].Br[C:54]1[CH:55]=[C:56]([O:62][CH3:63])[C:57]([F:61])=[C:58]([F:60])[CH:59]=1.[CH3:64][O:65][C:66]1[CH:71]=[CH:70][C:69]([O:72][CH3:73])=[CH:68][C:67]=1[C:74](=[O:76])[CH3:75]>C1COCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O>[F:60][C:58]1[CH:59]=[C:54]([CH2:75][C:74]([C:67]2[CH:68]=[C:69]([O:72][CH3:73])[CH:70]=[CH:71][C:66]=2[O:65][CH3:64])=[O:76])[CH:55]=[C:56]([O:62][CH3:63])[C:57]=1[F:61]

Komponenten

8

Edukt 4

HCID 709912',5'-DimethoxyacetophenoneHCID 634876Binap, (A+-)-HCID 27732885-Bromo-1,2-difluoro-3-methoxybenzeneHCID 23676156Sodium t-butoxide

Produkt 1

HCID 866828992-(3,4-Difluoro-5-methoxyphenyl)-1-(2,5-dimethoxyphenyl)ethanoneAusbeute 24,8 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 9811564Bis(dibenzylideneacetone)palladiumKatalysatorHCID 962WaterLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
70 °C

Versuchsvorschrift

A 100-mL round-bottom flask charged with Pd2dba3 (69 mg, 0.075 mmol), BINAP (112 mg, 0.18 mmol), and NaOt−Bu (650 mg, 6.5 mmol) was degassed and filled with N2. THF (20 mL) was added, followed by a solution 5-bromo-1,2-difluoro-3-methoxybenzene (1.1 g, 5 mmol) and 1-(2,5-dimethoxyphenyl)ethanone (1.08 g, 6 mmol) in THF (10 mL). The resulting mixture was heated at 70° C. for 16 h. Water (30 mL) was added, and the mixture was extracted with ether (3×50 mL). The combined organics were dried over anhydrous Na2SO4, filtered, and concentrated to give the crude product, which was purified by column chromatography on silica gel (eluting with petroleum ether/ethyl acetate=80/1˜40/1) to give 2-(3,4-difluoro-5-methoxyphenyl)-1-(2,5-dimethoxyphenyl)ethanone (0.4 g) as a light yellow solid. 1H NMR (CDCl3): δ 7.24 (d, 1H), 7.04 (dd, 1H), 6.92 (d, 1H), 6.68-6.61 (m, 2H), 4.23 (s, 2H), 3.90 (s, 3H), 3.87 (s, 3H), 3.78 (s, 3H); LCMS: 323 (M+H)+.

Aufarbeitung

  1. customwas degassed
  2. additionfilled with N2
  3. additionTHF (20 mL) was added
  4. extractionthe mixture was extracted with ether (3×50 mL)
  5. dry with materialThe combined organics were dried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customto give the crude product, which
  9. customwas purified by column chromatography on silica gel (eluting with petroleum ether/ethyl acetate=80/1˜40/1)

Quellen und Nachweise

ORD-Eintrag
ord-7bd0cafdf63846728732f4335e7acbf6
Quelldatensatz
uspto-grants-2014_04
Patentnummer
US08703810B2

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