4-Cyanopyridine → 4-(2,5-Difluorobenzoyl)pyridine

HRID 273733

Reaktionsgleichung

Reaktionsgleichung von HRID 273733
C([Li])CCC.CN(C)[CH2:8][CH2:9][N:10](C)[CH2:11][CH2:12]N(C)C.[F:18][C:19]1[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=1.C(C1C=CN=CC=1)#N.C1C[O:37][CH2:36][CH2:35]1>>[F:18][C:19]1[CH:24]=[CH:23][C:22]([F:25])=[CH:21][C:20]=1[C:36]([C:35]1[CH:8]=[CH:9][N:10]=[CH:11][CH:12]=1)=[O:37]

Komponenten

6

Edukt 5

HCID 75064-CyanopyridineHCID 8028Tetrahydrofuran3×HCID 108921,4-DifluorobenzeneHCID 18196PentamethyldiethylenetriamineHCID 178418339Butyllithium

Produkt 1

HCID 189984524-(2,5-Difluorobenzoyl)pyridineAusbeute 51,5 %

Reaktionsbedingungen

Temperatur
-75 °C

Versuchsvorschrift

Butyl lithium (70 ml of 2.22M solution, 155 mmole) was added to a solution of pentamethyldiethylenetriamine (23.3 ml, 155 mmole) in THF (250 ml) at -70° C. The solution was stirred for 5 min and 1,4-difluorobenzene (17.7 g, 155 mmole) in THF was added at -70° C. The solution was stirred for 2 hr during which time it was cooled to -75° C. and 4-cyanopyridine (15.6 g, 150 mmole) in THF was added at -75° C. The mixture was allowed to warm to 25° C. slowly and then quenched with ammonium chloride solution. The mixture was diluted with ether and the organic layer was separated. The organic layer was washed with water and 3N hydrochloric acid. The acid washes were stirred for 2 hr and basified with sodium hydroxide. The basic mixture was extracted with ether and the ether solution concentrated in vacuo. The crude product was purified by chromatography on silica eluting with ethyl acetate-hexane (20:1) to give 4-(2,5-difluorobenzoyl)pyridine (16.9 g, 51.5%).

Aufarbeitung

  1. stirringThe solution was stirred for 2 hr during which time it
  2. temperatureto warm to 25° C. slowly
  3. customquenched with ammonium chloride solution
  4. additionThe mixture was diluted with ether
  5. customthe organic layer was separated
  6. washThe organic layer was washed with water and 3N hydrochloric acid
  7. stirringThe acid washes were stirred for 2 hr and basified with sodium hydroxide
  8. extractionThe basic mixture was extracted with ether
  9. concentrationthe ether solution concentrated in vacuo
  10. customThe crude product was purified by chromatography on silica eluting with ethyl acetate-hexane (20:1)

Quellen und Nachweise

ORD-Eintrag
ord-d4313a586a554ae8967446c481bfa571
Quelldatensatz
uspto-grants-1995_02
Patentnummer
US05387593

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