Epichlorohydrin → 3-(3,4-dichloro-phenyl)-1-oxiranylmethyl-1H-pyrazole

HRID 2220509Notes

Reaction equation

HRID 2220509 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:13]=[CH:12][NH:11][N:10]=2)[CH:5]=[CH:6][C:7]=1[Cl:8].C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:20]([CH:22]1[O:24][CH2:23]1)Cl>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([C:9]2[CH:13]=[CH:12][N:11]([CH2:20][CH:22]3[CH2:23][O:24]3)[N:10]=2)[CH:5]=[CH:6][C:7]=1[Cl:8]

Participants

5

Reactant 3

HCID 7835EpichlorohydrinHCID 10796Cesium carbonateHCID 178477946HCID 178477946, compound

Product 1

HCID 179754053-(3,4-dichloro-phenyl)-1-oxiranylmethyl-1H-pyrazoleYield 82%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A stirred solution of 3-(3,4-dichlorophenyl)pyrazole (300 mg, 1.4 mmol) in DMF (5 mL) was treated with cesium carbonate (550 mg, 1.69 mmol) and epichlorohydrin (1.1 mL, 14.0 mmol) at room temperature for 18 h. The crude reaction mixture was then partitioned between EtOAc (50 mL) and water (35 mL). The aqueous phase was further extracted (2×50 mL) and the combined organic layers were washed with brine, dried (Na2SO4), filtered and concentrated under reduced pressure to yield crude product. Purification by column chromatography (silica, 25% EtOAc/hexanes) afforded 308 mg (82%) of the title compound. 1NMR (400 MHz, CDCl3): 7.83 (d, J=2 Hz, 1H), 7.54 (dd, J=2, 8 Hz, 1H), 7.44 (d, J=2 Hz, 1H), 7.38 (d, J=8 Hz, 1H), 6.48 (d, J=2 Hz, 1H), 4.45 (dd, J=3, 9.7 Hz, 1H), 4.12 (dd, J=6, 15 Hz, 1H), 3.31 (m, 1H), 2.81 (dd, J=4.0, 4.6 Hz, 1H), 2.47 (dd, J=2.6, 4.7 Hz, 1H).

Workup

  1. customThe crude reaction mixture
  2. customwas then partitioned between EtOAc (50 mL) and water (35 mL)
  3. extractionThe aqueous phase was further extracted (2×50 mL)
  4. washthe combined organic layers were washed with brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customto yield crude product
  9. customPurification by column chromatography (silica, 25% EtOAc/hexanes)

Sources & evidence

ORD record
ord-0b013c434fb64e81b44a1427abe9d0d2
Source dataset
uspto-grants-2008_08
Patent number
US07417046B2

Reaction notes

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