Cesium carbonate → 5-(3,3-Difluoroazetidin-1-yl)-4-(2,2,2-trifluoroethoxy)picolinonitrile

HRID 1480287Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1480287
Br[C:2]1[C:3]([O:10][CH2:11][C:12]([F:15])([F:14])[F:13])=[CH:4][C:5]([C:8]#[N:9])=[N:6][CH:7]=1.Cl.[F:17][C:18]1([F:22])[CH2:21][NH:20][CH2:19]1.C(=O)([O-])[O-].[Cs+].[Cs+].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>C1(C)C=CC=CC=1.C([O-])(=O)C.C([O-])(=O)C.[Pd+2]>[F:17][C:18]1([F:22])[CH2:21][N:20]([C:2]2[C:3]([O:10][CH2:11][C:12]([F:15])([F:14])[F:13])=[CH:4][C:5]([C:8]#[N:9])=[N:6][CH:7]=2)[CH2:19]1

Komponenten

7

Edukt 4

HCID 10796Cesium carbonateHCID 634876Binap, (A+-)-HCID 27582473,3-Difluoroazetidine hydrochlorideHCID 902033795-Bromo-4-(2,2,2-trifluoroethoxy)picolinonitrile

Produkt 1

HCID 902032995-(3,3-Difluoroazetidin-1-yl)-4-(2,2,2-trifluoroethoxy)picolinonitrileAusbeute 78,3 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 167845palladium(II) acetateKatalysatorHCID 1140TolueneLösungsmittel

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

To a solution of 5-Bromo-4-(2,2,2-trifluoro-ethoxy)-pyridine-2-carbonitrile (example 78c, 587 mg, 2.09 mmol) in dry toluene (10 ml) in a schlenk tube was added 3,3-difluoroazetidine hydrochloride (298 mg, 2.3 mmol), cesium carbonate (1.36 g, 4.18 mmol), palladium diacetate (46.9 mg, 209 μmol) and BINAP (130 mg, 209 μmol). The reaction mixture was stirred at 120° C. for 1 hour. The reaction mixture was filtered over a pad of celite and the filtrate was diluted with ethylacetate. The organic phase was extracted with a 1M aqueous solution of sodium bicarbonate. The organic phase was dried over sodium sulfate and evaporated down to dryness. The crude material was purified by flash chromatography on silica eluting with a heptane/ethyl acetate gradient to yield the title compound (480 mg, 78%). MS (ESI, m/z): 294.2 (M+H+).

Aufarbeitung

  1. filtrationThe reaction mixture was filtered over a pad of celite
  2. additionthe filtrate was diluted with ethylacetate
  3. extractionThe organic phase was extracted with a 1M aqueous solution of sodium bicarbonate
  4. dry with materialThe organic phase was dried over sodium sulfate
  5. customevaporated down to dryness
  6. customThe crude material was purified by flash chromatography on silica eluting with a heptane/ethyl acetate gradient

Quellen und Nachweise

ORD-Eintrag
ord-bbeabb260d3946b39ccd2850af87b62e
Quelldatensatz
uspto-grants-2016_08
Patentnummer
US09409866B2

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