Potassium Phosphate, Tribasic → 5-[4-(benzyloxy)biphenyl-3-yl]-1-methyl-1H-pyrazole

HRID 1619709Notes

Reaction equation

HRID 1619709 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.[CH3:22][N:23]1[C:27](B(O)O)=[CH:26][CH:25]=[N:24]1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:9]([O:8][C:7]1[CH:6]=[CH:5][C:4]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[CH:3][C:2]=1[C:27]1[N:23]([CH3:22])[N:24]=[CH:25][CH:26]=1)[C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1

Participants

8

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 75806TricyclohexylphosphineHCID 11182610(1-methyl-1H-pyrazol-5-yl)boronic acidHCID 57535037Benzyl 3-bromobiphenyl-4-yl ether

Product 1

HCID 580422625-[4-(benzyloxy)biphenyl-3-yl]-1-methyl-1H-pyrazoleYield 63.9%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

A solution of benzyl 3-bromobiphenyl-4-yl ether (500 mg, 1.47 mmol) and (1-methyl-1H-pyrazol-5-yl)boronic acid (185 mg, 1.47 mmol) in dioxane (4 mL) was degassed with argon for 30 minutes. Tris(dibenzylideneacetone)dipalladium (0) (54 mg, 0.06 mmol) and tricyclohexylphosphine (33 mg, 0.12 mmol) were added to the mixture under an argon atmosphere. A degassed solution of tripotassium phosphate (626 mg, 2.95 mmol) in water (2 mL) was added and the mixture was stirred at reflux for 16 hours under an argon atmosphere. The cooled reaction mixture was filtered through a pad of Celite and the filtrate evaporated in vacuo. The residue was dissolved in ethyl acetate (25 mL) and the solution was washed with water (2×10 mL), brine (10 mL), dried over Na2SO4, filtered and evaporated. The residue was purified by silica gel column chromatography (10% ethyl acetate in hexane) to afforded the title compound (320 mg).

Workup

  1. temperatureat reflux for 16 hours under an argon atmosphere
  2. customThe cooled reaction mixture
  3. filtrationwas filtered through a pad of Celite
  4. customthe filtrate evaporated in vacuo
  5. dissolutionThe residue was dissolved in ethyl acetate (25 mL)
  6. washthe solution was washed with water (2×10 mL), brine (10 mL)
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. customevaporated
  10. customThe residue was purified by silica gel column chromatography (10% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-3cbad440a0c649e1b2603d2239e95834
Source dataset
uspto-grants-2014_07
Patent number
US08772293B2

Reaction notes

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