Pyridine → 6-{4-[2-(Trifluoromethyl)phenoxy]piperidin-1-yl}pyridazine-3-carbonitrile

HRID 1714875Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1714875
[F:1][C:2]([F:26])([F:25])[C:3]1[CH:24]=[CH:23][CH:22]=[CH:21][C:4]=1[O:5][CH:6]1[CH2:11][CH2:10][N:9]([C:12]2[N:17]=[N:16][C:15]([C:18]([NH2:20])=O)=[CH:14][CH:13]=2)[CH2:8][CH2:7]1.N1C=CC=CC=1.FC(F)(F)C(OC(=O)C(F)(F)F)=O.C([O-])(O)=O.[Na+]>O1CCOCC1.C(OCC)(=O)C>[F:25][C:2]([F:1])([F:26])[C:3]1[CH:24]=[CH:23][CH:22]=[CH:21][C:4]=1[O:5][CH:6]1[CH2:11][CH2:10][N:9]([C:12]2[N:17]=[N:16][C:15]([C:18]#[N:20])=[CH:14][CH:13]=2)[CH2:8][CH2:7]1

Komponenten

7

Edukt 4

HCID 1049PyridineHCID 9845Trifluoroacetic anhydrideHCID 516892Sodium BicarbonateHCID 462254256-(4-(2-(Trifluoromethyl)phenoxy)piperidin-1-yl)pyridazine-3-carboxamide

Produkt 1

HCID 685040226-{4-[2-(Trifluoromethyl)phenoxy]piperidin-1-yl}pyridazine-3-carbonitrile

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 8857Ethyl AcetateLösungsmittelHCID 312751,4-DioxaneLösungsmittel

Versuchsvorschrift

To a solution of 6-{4-[2-(trifluoromethyl)phenoxy]piperidin-1-yl}pyridazine-3-carboxamide (1.35 g, 3.69 mmol) and pyridine (1.49 mL, 18.43 mmol) in 1,4-dioxane (30 mL) at 0° C. was added trifluoroacetic anhydride (1.04 mL, 7.37 mmol). The mixture was warmed to room temperature and stirred for 2 days. Aqueous saturated NaHCO3 and ethyl acetate were added. The layers were separated and the aqueous phase was extracted four times with ethyl acetate. The combined organic extracts were washed with brine, dried (NaSO4) and concentrated. Purification by silica gel chromatography (gradient 60% ethyl acetate:hexanes to 100% ethyl acetate) provided the title compound. 1H NMR (acetone-d6) δ 7.75 (1H, d, J=9.6 Hz), 7.68-7.62 (2H, m), 7.37 (2H, dd, J=8.4, 13.9 Hz), 7.13 (1H, t, J=7.6 Hz), 5.08-5.04 (1H, m), 4.06-4.02 (4H, m), 2.20-2.14 (2H, m), 2.00-1.94 (2H, m).

Aufarbeitung

  1. customThe layers were separated
  2. extractionthe aqueous phase was extracted four times with ethyl acetate
  3. washThe combined organic extracts were washed with brine
  4. dry with materialdried (NaSO4)
  5. concentrationconcentrated
  6. customPurification by silica gel chromatography (gradient 60% ethyl acetate:hexanes to 100% ethyl acetate)

Quellen und Nachweise

ORD-Eintrag
ord-4641f3063dfc46069c2acffaf8e75f3b
Quelldatensatz
uspto-grants-2010_09
Patentnummer
US07799787B2

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