Pyridine → ethyl 1-(4-(1,3,4-oxadiazol-2-yl)phenyl)-3-tert-butyl-1H-pyrazole-5-carboxylate

HRID 1930430Notes

Reaction equation

HRID 1930430 reaction equation
[O:1]1[CH:5]=[N:4][N:3]=[C:2]1[C:6]1[CH:11]=[CH:10][C:9](B(O)O)=[CH:8][CH:7]=1.[C:15]([C:19]1[CH:23]=[C:22]([C:24]([O:26][CH2:27][CH3:28])=[O:25])[NH:21][N:20]=1)([CH3:18])([CH3:17])[CH3:16].N1C=CC=CC=1>C(Cl)Cl.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[O:1]1[CH:5]=[N:4][N:3]=[C:2]1[C:6]1[CH:11]=[CH:10][C:9]([N:21]2[C:22]([C:24]([O:26][CH2:27][CH3:28])=[O:25])=[CH:23][C:19]([C:15]([CH3:16])([CH3:18])[CH3:17])=[N:20]2)=[CH:8][CH:7]=1

Participants

6

Reactant 3

HCID 1049PyridineHCID 2743509Ethyl 3-tert-butyl-1H-pyrazole-5-carboxylateHCID 10219751[4-(1,3,4-oxadiazol-2-yl)phenyl]boronic Acid

Product 1

HCID 69036833ethyl 1-(4-(1,3,4-oxadiazol-2-yl)phenyl)-3-tert-butyl-1H-pyrazole-5-carboxylateYield 100%

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalystHCID 6344DichloromethaneSolvent

Procedure

A mixture of 4-(1,3,4-oxadiazol-2-yl)phenylboronic acid (303 mg, 1.60 mmol) and powdered 4A molecular sieves (300 mg) in CH2Cl2 (6 mL) was heated to reflux for 2 h. Ethyl 3-tert-butyl-1H-pyrazole-5-carboxylate (310 mg, 1.6 mmol), pyridine (0.13 mL, 1.6 mmol) and copper (II) acetate (290 mg, 1.6 mmol) were added and the reaction mixture was refluxed for 24 h. The reaction was filtered and the solid was washed with EtOAc (40 mL) and MeOH (40 mL). The combined filtrate and washings were concentrated in vacuo and partitioned between EtOAc (40 mL) and water (20 mL). The organics were washed with water (20 mL), satd aq NaHCO3 (20 mL), water (20 mL), and brine (20 mL), dried (Na2SO4) and concentrated in vacuo. The oily residue was chromatographed to provide ethyl 1-(4-(1,3,4-oxadiazol-2-yl)phenyl)-3-tert-butyl-1H-pyrazole-5-carboxylate (440 mg, > 100% yield) as a visocus oil contaminated with the starting ester. The mixture was used without further purification.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 2 h
  3. temperaturethe reaction mixture was refluxed for 24 h
  4. filtrationThe reaction was filtered
  5. washthe solid was washed with EtOAc (40 mL) and MeOH (40 mL)
  6. concentrationThe combined filtrate and washings were concentrated in vacuo
  7. custompartitioned between EtOAc (40 mL) and water (20 mL)
  8. washThe organics were washed with water (20 mL)
  9. dry with materialdried (Na2SO4)
  10. concentrationconcentrated in vacuo
  11. customThe oily residue was chromatographed

Sources & evidence

ORD record
ord-34af821dcf39479c960679bd9eb300b0
Source dataset
uspto-grants-2012_05
Patent number
US08188113B2

Reaction notes

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