Citric Acid → 5-tert-butyl-1-(2'-chloro-1,1'-biphenyl-3-yl)-1H-pyrazole-3-carboxylic acid

HRID 733127

Reaction equation

HRID 733127 reaction equation
Br[C:2]1[CH:3]=[C:4]([N:8]2[C:12]([C:13]([CH3:16])([CH3:15])[CH3:14])=[CH:11][C:10]([C:17]([O:19]CC)=[O:18])=[N:9]2)[CH:5]=[CH:6][CH:7]=1.[Cl:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1B(O)O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+].[OH-].[Na+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>C(O)CC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[C:13]([C:12]1[N:8]([C:4]2[CH:3]=[C:2]([C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=3[Cl:22])[CH:7]=[CH:6][CH:5]=2)[N:9]=[C:10]([C:17]([OH:19])=[O:18])[CH:11]=1)([CH3:15])([CH3:16])[CH3:14]

Participants

10

Reactant 6

HCID 311Citric AcidHCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 14798Sodium HydroxideHCID 27343222-Chlorophenylboronic acidHCID 57428253ethyl 1-(3-bromophenyl)-5-tert-butyl-1H-pyrazole-3-carboxylate

Product 1

HCID 112796905-tert-butyl-1-(2'-chloro-1,1'-biphenyl-3-yl)-1H-pyrazole-3-carboxylic acid

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 10311-PropanolSolvent

Procedure

To a solution of ethyl 1-(3-bromophenyl)-5-tert-butyl-1H-pyrazole-3-carboxylate and 2-chlorophenylboronic acid (0.279 g, 1.78 mmol) in n-propanol:water (2.35 ml:0.482 ml) mixture were added palladium acetate (0.005 g), triphenylphosphine (0.016 g) and 2N sodium carbonate (0.497 ml) and the solution was refluxed for 16 hours. To the reaction, a 2N solution of NaOH (1.5 ml) was added and refluxed for an additional 2 hours. The solution was cooled, acidified with 10% citric acid and extracted into ethyl acetate. The organic phase was washed with brine, dried over sodium sulfate, filtered and concentrated to give 0.212 g of 5-tert-butyl-1-(2′-chloro-1,1′-biphenyl-3-yl)-1H-pyrazole-3-carboxylic acid.

Workup

  1. temperaturethe solution was refluxed for 16 hours
  2. customTo the reaction
  3. temperaturerefluxed for an additional 2 hours
  4. temperatureThe solution was cooled
  5. extractionextracted into ethyl acetate
  6. washThe organic phase was washed with brine
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-3b54fcb58b5f418dbddf2a237380cde7
Source dataset
uspto-grants-2009_09
Patent number
US07589116B2

Linked notes

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