Isoamyl Nitrite → 5-[4-(benzyloxy)phenyl]-3-chloro-1-(4-methoxyphenyl)-1H-pyrazole

HRID 351273Notes

Reaction equation

HRID 351273 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[N:19]([C:20]3[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=3)[N:18]=[C:17](N)[CH:16]=2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl-:29].[Li+].N(OCCC(C)C)=O.[Cl-].[NH4+]>C(#N)C.[Cu](Cl)Cl.C(OCC)(=O)C>[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15]2[N:19]([C:20]3[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][CH:21]=3)[N:18]=[C:17]([Cl:29])[CH:16]=2)=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 8053Isoamyl NitriteHCID 25517Ammonium ChlorideHCID 433294Lithium ChlorideHCID 210909885-[4-(Benzyloxy)phenyl]-1-(4-methoxyphenyl)-1H-pyrazol-3-amine

Product 1

HCID 210909015-[4-(benzyloxy)phenyl]-3-chloro-1-(4-methoxyphenyl)-1H-pyrazoleYield 66.8%

Reagents, catalysts & solvents 3

HCID 24014Cupric ChlorideCatalystHCID 6342AcetonitrileSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 5-[4-(benzyloxy)phenyl]-3-amino-1-(4-methoxyphenyl)-1H-pyrazole (4.0 g), lithium chloride (2.28 g), and copper(II) chloride (2.90 g) in acetonitrile (50 ml) was stirred at ambient temperature for 10 minutes. To this mixture was added isoamyl nitrite (2.52 g), and the mixture was stirred at ambient temperature for 1.5 hours. To the reaction mixture was added a mixture of ethyl acetate and saturated aqueous ammonium chloride solution. The mixture was stirred at ambient temperature for a while, and partitioned. The aqueous layer was reextracted with ethyl acetate. The combined organic layers were washed with saturated aqueous ammonium chloride solution and saturated aqueous sodium chloride solution, dried over magnesium sulfate, and concentrated in vacuo. The residue was purified by silica gel column chromatography eluted with 20% AcOEt/n-hexane. The pure fractions were collected and concentrated in vacuo to give 5-[4-(benzyloxy)phenyl]-3-chloro-1-(4-methoxyphenyl)-1H-pyrazole (2.81 g) as a solid.

Workup

  1. stirringthe mixture was stirred at ambient temperature for 1.5 hours
  2. additionTo the reaction mixture was added
  3. stirringThe mixture was stirred at ambient temperature for a while
  4. custompartitioned
  5. washThe combined organic layers were washed with saturated aqueous ammonium chloride solution and saturated aqueous sodium chloride solution
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by silica gel column chromatography
  9. washeluted with 20% AcOEt/n-hexane
  10. customThe pure fractions were collected
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-01cb74ecaa10412f8af73bbe5ec45c84
Source dataset
uspto-grants-2007_02
Patent number
US07183306B2

Reaction notes

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