Sodium Carbonate → 1-Phenyl-5-(3-(trifluoromethoxy)phenyl)-1H-pyrazol-3-ylamine

HRID 83491Notes

Reaction equation

HRID 83491 reaction equation
I[C:2]1[N:6]([C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=2)[N:5]=[C:4]([NH2:13])[CH:3]=1.[F:14][C:15]([F:27])([F:26])[O:16][C:17]1[CH:18]=[C:19](B(O)O)[CH:20]=[CH:21][CH:22]=1.C(=O)([O-])[O-].[Na+].[Na+].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.C(=O)([O-])O.[Na+]>COCCOC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:7]1([N:6]2[C:2]([C:19]3[CH:20]=[CH:21][CH:22]=[C:17]([O:16][C:15]([F:14])([F:26])[F:27])[CH:18]=3)=[CH:3][C:4]([NH2:13])=[N:5]2)[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1

Participants

8

Reactant 5

HCID 10340Sodium CarbonateHCID 75806TricyclohexylphosphineHCID 516892Sodium BicarbonateHCID 27343853-(Trifluoromethoxy)phenylboronic Acid (contains varying amounts of Anhydride)HCID 86680350HCID 86680350, compound

Product 1

HCID 712877301-Phenyl-5-(3-(trifluoromethoxy)phenyl)-1H-pyrazol-3-ylamineYield 44%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

To a solution of 5-iodo-1-phenyl-1H-pyrazol-3-ylamine (605 mg) in ethylene glycol dimethyl ether (12 ml) were sequentially added 3-(trifluoromethoxy)phenyl boronic acid (481 mg), a 2M aqueous solution of sodium carbonate (6 ml), tricyclohexylphosphine (119 mg), palladium acetate (48 mg), and the mixture was stirred for 2 hours at reflux. This reaction mixture was cooled to room temperature, and a saturated aqueous solution of sodium hydrogen carbonate was added thereto, and then the mixture was filtered through Celite. The filtrate was extracted with ethyl acetate. The resulting organic layer was washed with a saturated aqueous solution of sodium chloride, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate=2/1) to give the titled compound (298 mg).

Workup

  1. temperatureat reflux
  2. filtrationthe mixture was filtered through Celite
  3. extractionThe filtrate was extracted with ethyl acetate
  4. washThe resulting organic layer was washed with a saturated aqueous solution of sodium chloride
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting residue was purified by silica gel column chromatography (eluent: n-hexane/ethyl acetate=2/1)

Sources & evidence

ORD record
ord-8b8b806c94904a039738a8eb683df116
Source dataset
uspto-grants-2014_09
Patent number
US08846746B2

Reaction notes

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