Potassium Carbonate → Ethyl 1-(3,4-difluorophenyl)-4[3-(ethoxycarbonyl)phenyl]-1H-pyrazole-3-carboxylate

HRID 587098Notes

Reaction equation

HRID 587098 reaction equation
Br[C:2]1[C:3]([C:15]([O:17][CH2:18][CH3:19])=[O:16])=[N:4][N:5]([C:7]2[CH:12]=[CH:11][C:10]([F:13])=[C:9]([F:14])[CH:8]=2)[CH:6]=1.CC1(C)C(C)(C)OB([C:28]2[CH:29]=[C:30]([CH:35]=[CH:36][CH:37]=2)[C:31]([O:33][CH3:34])=[O:32])O1.[C:39](=O)([O-])[O-].[K+].[K+]>C(O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[F:14][C:9]1[CH:8]=[C:7]([N:5]2[CH:6]=[C:2]([C:36]3[CH:37]=[CH:28][CH:29]=[C:30]([C:31]([O:33][CH2:34][CH3:39])=[O:32])[CH:35]=3)[C:3]([C:15]([O:17][CH2:18][CH3:19])=[O:16])=[N:4]2)[CH:12]=[CH:11][C:10]=1[F:13]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 27346513-Methoxycarbonylphenylboronic acid pinacol esterHCID 89464890ethyl 4-bromo-1-(3,4-difluorophenyl)-1H-pyrazole-3-carboxylate

Product 1

HCID 89464679Ethyl 1-(3,4-difluorophenyl)-4[3-(ethoxycarbonyl)phenyl]-1H-pyrazole-3-carboxylate

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 702EthanolSolvent

Procedure

180 mg (0.54 mmol) of ethyl 4-bromo-1-(3,4-difluorophenyl)-1H-pyrazole-3-carboxylate, 156.7 mg (0.59 mmol) of methyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate, 158 mg (1.14 mmol) of potassium carbonate, 5.07 mg (0.011 mmol) of 2,2-dicyclohexylphosphino-2″,6″-diisopropoxybiphenyl and 1.22 mg (0.005 mmol) of palladium (II)acetate were suspended in 5 ml of ethanol and heated at the boil for 4 h. After cooling to room temperature, the solvent was removed under reduced pressure, the residue was dissolved in water and dichloromethane, the phases were separated and the organic phase was dried over magnesium sulfate. The crude product was purified by chromatography (ethyl acetate:n-heptane 1:4). This gave 84 mg (37%) of the desired product. 1H-NMR (400 MHz, CDCl3 δ, ppm) 8.15 (s, 1H); 8.05 (d, 1H); 7.96 (s, 1H); 7.74-7.69 (m, 2H); 7.53-7.47 (m, 2H); 7.28 (m, 1H); 4.48-4.34 (m, 4H); 1.43 (t, 3H); 1.29 (t, 3H)

Workup

  1. temperatureheated at the boil for 4 h
  2. customthe solvent was removed under reduced pressure
  3. dissolutionthe residue was dissolved in water
  4. customdichloromethane, the phases were separated
  5. dry with materialthe organic phase was dried over magnesium sulfate
  6. customThe crude product was purified by chromatography (ethyl acetate:n-heptane 1:4)

Sources & evidence

ORD record
ord-d81fe33f664741ed9f685641a0ae0dee
Source dataset
uspto-grants-2016_01
Patent number
US09226505B2

Reaction notes

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