Potassium Carbonate → 5-(2,6-difluoro-phenoxy)-2-(tetrahydro-pyran-2-yl)-2H-pyridazin-3-one

HRID 2381298Notes

Reaction equation

HRID 2381298 reaction equation
I[C:2]1[CH:7]=[N:6][N:5]([CH:8]2[CH2:13][CH2:12][CH2:11][CH2:10][O:9]2)[C:4](=[O:14])[CH:3]=1.[F:15][C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[C:17]=1[OH:23].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.O>[F:15][C:16]1[CH:21]=[CH:20][CH:19]=[C:18]([F:22])[C:17]=1[O:23][C:2]1[CH:7]=[N:6][N:5]([CH:8]2[CH2:13][CH2:12][CH2:11][CH2:10][O:9]2)[C:4](=[O:14])[CH:3]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 943922,6-DifluorophenolHCID 579192495-Iodo-2-(tetrahydro-2H-pyran-2-yl)pyridazin-3(2H)-one

Product 1

HCID 668753985-(2,6-difluoro-phenoxy)-2-(tetrahydro-pyran-2-yl)-2H-pyridazin-3-oneYield 49%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

A solution of 5-iodo-2-(tetrahydro-pyran-2-yl)-2H-pyridazin-3-one (204 mg, 0.67 mmol) in anhydrous N,N-dimethylformamide (8.5 mL, 0.08M) was treated with 2,6-difluorophenol (0.09 g, 0.69 mmol) and potassium carbonate (0.20 g, 1.45 mmol). The reaction was heated at 120° C. overnight. At this time, the reaction was diluted with water (25 mL) and extracted with methylene chloride (3×25 mL). The combined organics were washed with a saturated aqueous sodium chloride solution (25 mL), dried over magnesium sulfate, filtered, rinsed, and concentrated in vacuo. Silica gel column chromatography (AnaLogix, 24 g, 20% to 40% ethyl acetate/hexanes) afforded 5-(2,6-difluoro-phenoxy)-2-(tetrahydro-pyran-2-yl)-2H-pyridazin-3-one (99.7 mg, 49%) as an off-white solid. 1H-NMR (400 MHz, DMSO-d6) δ ppm 1.43-1.56 (m, 2H), 1.57-1.76 (m, 2H), 1.88-2.01 (m, 1H), 2.01-2.16 (m, 1H), 3.53-3.63 (m, 1H), 3.90-3.98 (m, 1H), 5.82 (dd, J=10.5, 1.6 Hz, 1H), 6.04 (d, J=2.7 Hz, 1H), 7.34-7.43 (m, 2H), 7.43-7.55 (m, 1H), 8.23 (d, J=2.7 Hz, 1H).

Workup

  1. extractionextracted with methylene chloride (3×25 mL)
  2. washThe combined organics were washed with a saturated aqueous sodium chloride solution (25 mL)
  3. dry with materialdried over magnesium sulfate
  4. filtrationfiltered
  5. washrinsed
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-9124ed193b6f4e29bc2c9c91727e1e04
Source dataset
uspto-grants-2012_09
Patent number
US08258134B2

Reaction notes

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