Sodium Carbonate → 6-Fluoro-3,4-dimethoxy-2-(2-pyridyl)benzonitrile

HRID 1582378Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1582378
[F:1][C:2]1[C:7]([C:8]#[N:9])=[C:6](I)[C:5]([O:11][CH3:12])=[C:4]([O:13][CH3:14])[CH:3]=1.B([O-])O[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=1.C(=O)([O-])[O-].[Na+].[Na+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Cu]I.C(OCC)(=O)C.O.O1CCOCC1>[F:1][C:2]1[C:7]([C:8]#[N:9])=[C:6]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][N:18]=2)[C:5]([O:11][CH3:12])=[C:4]([O:13][CH3:14])[CH:3]=1

Komponenten

10

Edukt 4

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 227212146-Fluoro-2-iodo-3,4-dimethoxybenzonitrileHCID 178514833HCID 178514833, Verbindung2×

Produkt 1

HCID 98138056-Fluoro-3,4-dimethoxy-2-(2-pyridyl)benzonitrileAusbeute 49,3 %

Reagenzien, Katalysatoren, Lösungsmittel 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)KatalysatorHCID 11979704Tetrakis(triphenylphosphine)palladiumKatalysatorHCID 962WaterLösungsmittelHCID 8857Ethyl AcetateLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Versuchsvorschrift

Under nitrogen, stirred dioxane (20 ml) at 80° C. was charged with 6-fluoro-2-iodo-3,4-dimethoxybenzonitrile from Example 1(a) (1.0 g, 3.3 mmol), tetrakis(triphenyl-phosphine) palladium(0) (0.19 g, 0.16 mmol), the pyridyl boronate from Example 1(b) (1.22 g, estimated to be 7.1 mmol), copper(I)iodide (0.25 g, 1.3 mmol), sodium carbonate (0.69 g, 6.5 mmol) and triphenylphosphine (0.17 g, 0.65 mmol) and the resulting brown slurry heated to reflux. Further portions of the pyridyl boronate were added at the following times after the reaction had reached reflux: 0.61 g after 30 mins; 0.61 g after 1 hour; 0.61 g after 1 hour 30 mins; 0.61 g after 2 hours 30 mins; 0.61 g after 3 hours; and 0.30 g after 4 hours. After a total of 5 hours at reflux the reaction was allowed to cool to room temperature, water (10 ml) and ethyl acetate (20 ml) were added and the resulting mixture allowed to stir for 15 mins. After this time, the mixture was filtered through Arbocel™ filter aid and the pad washed with ethyl acetate (20 ml). The phases were separated and the aqueous phase extracted with ethyl acetate (20 ml). The organic phases were combined and evaporated to a brown oil. Acetonitrile was added, the mixture warmed to reflux and left to cool to room temperature overnight. The resulting suspension was filtered to give a cream solid that was dried in vacuo overnight at 45° C. to give 0.42 g of the title product (49%).

Aufarbeitung

  1. temperaturehad reached reflux
  2. wait0.61 g after 1 hour
  3. wait0.61 g after 1 hour 30 mins
  4. wait0.61 g after 2 hours 30 mins
  5. wait0.61 g after 3 hours
  6. waitand 0.30 g after 4 hours
  7. temperatureAfter a total of 5 hours at reflux the reaction
  8. filtrationAfter this time, the mixture was filtered through Arbocel™
  9. filtrationfilter aid
  10. washthe pad washed with ethyl acetate (20 ml)
  11. customThe phases were separated
  12. extractionthe aqueous phase extracted with ethyl acetate (20 ml)
  13. customevaporated to a brown oil
  14. additionAcetonitrile was added
  15. temperaturethe mixture warmed
  16. temperatureto reflux
  17. waitleft
  18. temperatureto cool to room temperature overnight
  19. filtrationThe resulting suspension was filtered
  20. customto give a cream solid
  21. customthat was dried in vacuo overnight at 45° C.

Quellen und Nachweise

ORD-Eintrag
ord-7495d308c9a040b6888f8539120b865f
Quelldatensatz
uspto-grants-2004_05
Patentnummer
US06734303B2

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