Potassium Carbonate → 4-chloro-2-(tetrahydro-pyran-2-yl)-5-(2-trifluoromethyl-phenoxy)-2H-pyridazin-3-one

HRID 2381481Notes

Reaction equation

HRID 2381481 reaction equation
[Cl:1][C:2]1[C:3](=[O:15])[N:4]([CH:9]2[CH2:14][CH2:13][CH2:12][CH2:11][O:10]2)[N:5]=[CH:6][C:7]=1Cl.C(=O)([O-])[O-].[K+].[K+].[F:22][C:23]([F:32])([F:31])[C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1[OH:30]>C(#N)C>[Cl:1][C:2]1[C:3](=[O:15])[N:4]([CH:9]2[CH2:14][CH2:13][CH2:12][CH2:11][O:10]2)[N:5]=[CH:6][C:7]=1[O:30][C:25]1[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=1[C:23]([F:22])([F:31])[F:32]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 679582-TrifluoromethylphenolHCID 107292624,5-Dichloro-2-(tetrahydro-pyran-2-yl)-2H-pyridazin-3-one2×

Product 1

HCID 668754514-chloro-2-(tetrahydro-pyran-2-yl)-5-(2-trifluoromethyl-phenoxy)-2H-pyridazin-3-oneYield 79.6%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
105 °C

Procedure

A solution of 4,5-dichloro-2-(tetrahydropyran-2-yl)-2H-pyridazin-3-one (4.00 g, 16.05 mmol) (Intermediate 20) in acetonitrile (178 mL, 0.09M) was treated with potassium carbonate (2.21 g, 16.05 mmol) and 2-trifluoromethyl-phenol (2.60 g, 16.05 mmol). The resulting reaction mixture was heated to 105° C. for 18 h and then was allowed to cool to 25° C. The reaction mixture was partitioned between water (150 mL) and methylene chloride (3×100 mL). The combined organics were dried over sodium sulfate, filtered and concentrated in vacuo. Silica gel column chromatography (AnaLogix) afforded 4-chloro-2-(tetrahydro-pyran-2-yl)-5-(2-trifluoromethyl-phenoxy)-2H-pyridazin-3-one (4.79 g, 79%) as a white solid; ES+-HRMS m/e calcd for C16H14N2O3F3Cl [M+H+] 375.0718, found 375.0718. 1H NMR (300 MHz, DMSO-d6) δ ppm 1.51 (d, 2H), 1.62-1.77 (m, 2H), 1.87-2.12 (m, 2H), 3.55-3.70 (m, 1H), 3.91-4.03 (m, 1H), 5.90 (dd, J=10.4, 2.0 Hz, 1H), 7.45-7.53 (m, 2H), 7.76 (t, J=7.8 Hz, 1H), 7.88 (d, J=7.5 Hz, 1H), 7.91 (s, 1H).

Workup

  1. customThe resulting reaction mixture
  2. temperatureto cool to 25° C
  3. customThe reaction mixture was partitioned between water (150 mL) and methylene chloride (3×100 mL)
  4. dry with materialThe combined organics were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-658947a3508946ea95db354d8cc5d09c
Source dataset
uspto-grants-2012_09
Patent number
US08258134B2

Reaction notes

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