Pyrazole → [3-(1H-Pyrazol-1-yl)phenyl]acetic acid

HRID 734504Notes

Reaction equation

HRID 734504 reaction equation
[NH:1]1[CH:5]=[CH:4][CH:3]=[N:2]1.C([O-])([O-])=O.[Cs+].[Cs+].[C@@H]1(N)CCCC[C@H]1N.CCCCCCCCCCCC.Br[C:33]1[CH:34]=[C:35]([CH2:39][C:40]([OH:42])=[O:41])[CH:36]=[CH:37][CH:38]=1.[OH-].[Na+]>O1CCOCC1.[Cu]I>[N:1]1([C:33]2[CH:34]=[C:35]([CH2:39][C:40]([OH:42])=[O:41])[CH:36]=[CH:37][CH:38]=2)[CH:5]=[CH:4][CH:3]=[N:2]1

Participants

9

Reactant 6

HCID 1048PyrazoleHCID 8182DodecaneHCID 10796Cesium carbonateHCID 14798Sodium HydroxideHCID 438061,2-Diaminocyclohexane, trans-HCID 74653(3-Bromophenyl)acetic acid

Product 1

HCID 21062671[3-(1H-Pyrazol-1-yl)phenyl]acetic acidYield 65%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 312751,4-DioxaneSolvent

Procedure

Pyrazole (1.2 eq), Cs2CO3 (2.5 eq), CuI (0.5 eq), trans-1,2-cyclohexanediamine (0.6 eq) and dodecane (1 eq), were added to a stirred solution of 3-bromophenylacetic acid (1 eq) in dioxane at room temperature under an inert atmosphere. The mixture was irradiated in a microwave reactor (PersonalChemistry Emrys™ Optimiser, 300 W, 160° C., 20 min), then added to a 1N aqueous solution of NaOH, and extracted with Et2O. The aqueous phase was acidified to pH=3 with HCl 2N, then extracted with ethyl acetate; this phase was washed with brine, dried over Na2SO4 and the solvent was removed under reduced pressure. The crude material was purified on SPE cartridge (Silica) eluting with a gradient from Cyclohexane/ethyl acetate 8:2, to Cyclohexane/ethyl acetate 1:1, affording the title compound in 65% yield.

Workup

  1. customThe mixture was irradiated in a microwave reactor (PersonalChemistry Emrys™ Optimiser, 300 W, 160° C., 20 min)
  2. extractionextracted with Et2O
  3. extractionextracted with ethyl acetate
  4. washthis phase was washed with brine
  5. dry with materialdried over Na2SO4
  6. customthe solvent was removed under reduced pressure
  7. customThe crude material was purified on SPE cartridge (Silica)
  8. washeluting with a gradient from Cyclohexane/ethyl acetate 8:2, to Cyclohexane/ethyl acetate 1:1

Sources & evidence

ORD record
ord-93996085208b4fb3a9d40ff3a68b1a60
Source dataset
uspto-grants-2009_09
Patent number
US07592346B2

Reaction notes

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