1-Propanol → Ethyl 5-methyl-1-{6-[2-(trifluoromethoxy)phenyl]pyridin-2-yl}-1H-pyrazole-3-carboxylate

HRID 733142Notes

Reaction equation

HRID 733142 reaction equation
[F:1][C:2]([F:14])([F:13])[O:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1B(O)O.Cl[C:16]1[N:21]=[C:20]([N:22]2[C:26]([CH3:27])=[CH:25][C:24]([C:28]([O:30][CH2:31][CH3:32])=[O:29])=[N:23]2)[CH:19]=[CH:18][CH:17]=1.C(O)CC.C(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1>[CH3:27][C:26]1[N:22]([C:20]2[CH:19]=[CH:18][CH:17]=[C:16]([C:5]3[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=3[O:3][C:2]([F:14])([F:13])[F:1])[N:21]=2)[N:23]=[C:24]([C:28]([O:30][CH2:31][CH3:32])=[O:29])[CH:25]=1

Participants

6

Reactant 4

HCID 10311-PropanolHCID 516892Sodium BicarbonateHCID 27772042-(Trifluoromethoxy)phenylboronic Acid (contains varying amounts of Anhydride)HCID 57428255Ethyl 1-(6-chloropyridin-2-yl)-5-methyl-1h-pyrazole-3-carboxylate

Product 1

HCID 11361317Ethyl 5-methyl-1-{6-[2-(trifluoromethoxy)phenyl]pyridin-2-yl}-1H-pyrazole-3-carboxylateYield 12.3%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

To the solution of 2-trifluoromethoxyphenyl boronic acid (0.192 g, 0.92 mmol) and the 2-chloropyridine compound from Step 1 (0.165 g, 0.62 mmol) in toluene:n-propanol (3 mL:3 mL) were added tetrabis(triphenylphosphine)palladium (0.072 g, 0.062 mmol) and aqueous sodium bicarbonate (2.0M, 0.62 mL, 1.2 mmol). The reaction mixture was stirred at 90° C. for 16 hours. After cooling to room temperature, the mixture was filtered through a Celite pad, and washed with ethyl acetate (3 times). The filtrate was concentrated. The resulting residue was dissolved in ethyl acetate and washed with saturated sodium carbonate aqueous solution and brine, the organic layer was dried over anhydrous sodium sulfate. After concentration, the crude product was applied to column chromatography on silica gel to afford the titled compound, as yellow oil, 30 mg, 12.3% yield.

Workup

  1. temperatureAfter cooling to room temperature
  2. filtrationthe mixture was filtered through a Celite pad
  3. washwashed with ethyl acetate (3 times)
  4. concentrationThe filtrate was concentrated
  5. dissolutionThe resulting residue was dissolved in ethyl acetate
  6. washwashed with saturated sodium carbonate aqueous solution and brine
  7. dry with materialthe organic layer was dried over anhydrous sodium sulfate
  8. concentrationAfter concentration

Sources & evidence

ORD record
ord-085e1e85050440d6a9a675a51ea65a7d
Source dataset
uspto-grants-2009_09
Patent number
US07589116B2

Reaction notes

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