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

HRID 1714875Notes

Reaction equation

HRID 1714875 reaction equation
[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

Participants

7

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-4641f3063dfc46069c2acffaf8e75f3b
Source dataset
uspto-grants-2010_09
Patent number
US07799787B2

Reaction notes

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