Potassium Carbonate → Methyl 6-{4-[2-(trifluoromethyl)phenoxy]piperidin-1-yl}pyridazine-3-carboxylate

HRID 1714863Notes

Reaction equation

HRID 1714863 reaction equation
Cl[C:2]1[N:7]=[N:6][C:5]([C:8]([O:10][CH3:11])=[O:9])=[CH:4][CH:3]=1.[F:12][C:13]([F:28])([F:27])[C:14]1[CH:26]=[CH:25][CH:24]=[CH:23][C:15]=1[O:16][CH:17]1[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]1.C(=O)([O-])[O-].[K+].[K+]>[I-].C([N+](CCCC)(CCCC)CCCC)CCC.O1CCOCC1>[F:28][C:13]([F:12])([F:27])[C:14]1[CH:26]=[CH:25][CH:24]=[CH:23][C:15]=1[O:16][CH:17]1[CH2:22][CH2:21][N:20]([C:2]2[N:7]=[N:6][C:5]([C:8]([O:10][CH3:11])=[O:9])=[CH:4][CH:3]=2)[CH2:19][CH2:18]1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 50187904-[2-(Trifluoromethyl)phenoxy]piperidineHCID 12379801Methyl 6-chloropyridazine-3-carboxylate

Product 1

HCID 68505610Methyl 6-{4-[2-(trifluoromethyl)phenoxy]piperidin-1-yl}pyridazine-3-carboxylate

Reagents, catalysts & solvents 2

HCID 67553Tetrabutylammonium IodideCatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of methyl 6-chloropyridazine-3-carboxylate (500 mg, 0.2.9 mmol), 4-[2-(trifluoromethyl)phenoxy]piperidine (851 mg, 0.3.5 mmol), potassium carbonate (802 mg, 5.8 mmol) and tetrabutylammonium iodide (20 mg, 0.06 mmol) in dioxane (30 mL) was refluxed for 24 h. After cooling, the mixture was filtered through celite, washed with EtOAc and concentrated. CombiFlash chromatography (40 g, 60-90% EtOAc in hexanes in 20 min, 35 mL/min, 18 mL/fraction) gave the title compound as a white solid. 1H NMR (400 MHz, acetone-d6): δ 1.93-1.99 (m, 2H), 2.14-2.20 (m, 2H), 3.93 (s, 3H), 3.97-4.09 (m, 4H), 5.03-5.07 (m, 1H), 7.13 (t, 1H), 7.31 (d, 1H), 7.40 (d, 1H), 7.65 (dd, 2H), 7.89 (d, 1H).

Workup

  1. temperaturewas refluxed for 24 h
  2. temperatureAfter cooling
  3. filtrationthe mixture was filtered through celite
  4. washwashed with EtOAc
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-7c54d2f1528e4434be448de42e372636
Source dataset
uspto-grants-2010_09
Patent number
US07799787B2

Reaction notes

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