Pyrazole → 2-Methoxy-4-(1H-pyrazol-1-yl)aniline

HRID 32797

Reaction equation

HRID 32797 reaction equation
Br[C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[C:4]([O:9][CH3:10])[CH:3]=1.[NH:11]1[CH:15]=[CH:14][CH:13]=[N:12]1.C([O-])([O-])=O.[K+].[K+].CN[C@H]1[C@H](NC)CCCC1.[Na+].[Cl-]>CN1C(=O)CCC1.[Cu]I.CCOC(C)=O>[CH3:10][O:9][C:4]1[CH:3]=[C:2]([N:11]2[CH:15]=[CH:14][CH:13]=[N:12]2)[CH:8]=[CH:7][C:5]=1[NH2:6]

Participants

9

Reactant 5

HCID 1048PyrazoleHCID 5234Sodium ChlorideHCID 11430Potassium CarbonateHCID 4592574-Bromo-2-methoxyanilineHCID 2733821trans-N,N'-dimethyl-1,2-cyclohexanediamine

Product 1

HCID 597943592-Methoxy-4-(1H-pyrazol-1-yl)anilineYield 90%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
150 °C

Procedure

To a solution of 4-bromo-2-(methyloxy)aniline (400 mg, 1.979 mmol) in anh. NMP (4 mL), at r.t., under N2, were added pyrazole (269 mg, 2 eq), K2CO3 (819 mg, 3 eq), CuI (377 mg, 1 eq) and (1R,2R)-diaminomethylcyclohexane (281 mg, 1 eq). The reaction mixture was stirred at 150° C. for 3 hr. It was cooled down to r.t. and poured into EtOAc/sat.aq. NaCl. The phases were separated and the organic layer was washed with sat.aq. NH4Cl (20 mL) and sat.aq. NaCl (20 mL). The combined aqueous layers were extracted back with EtOAc (20 mL) and the combined organic extracts were dried over anh. Na2SO4. The solids were filtered and the solvent evaporated. The crude product was purified by flash chromatography (silica gel, cHex/EtOAc 7:3) to give the title compound as a brown oil (336 mg, 90%)

Workup

  1. temperatureIt was cooled down to r.t.
  2. customThe phases were separated
  3. washthe organic layer was washed with sat.aq
  4. extractionThe combined aqueous layers were extracted back with EtOAc (20 mL)
  5. dry with materialthe combined organic extracts were dried over anh. Na2SO4
  6. filtrationThe solids were filtered
  7. customthe solvent evaporated
  8. customThe crude product was purified by flash chromatography (silica gel, cHex/EtOAc 7:3)

Sources & evidence

ORD record
ord-9dae480e5d5e4f97b07f3895141283dc
Source dataset
uspto-grants-2008_09
Patent number
US07427630B2

Linked notes

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