Dimethylformamide → 3-(3-fluoro-5chloro-2-pyridyl)-5-difluoromethoxy-1-methyl-[1H]-pyrazole

HRID 650484Notes

Reaction equation

HRID 650484 reaction equation
[F:1][C:2]1[C:3]([C:9]2[CH:13]=[C:12]([OH:14])[N:11]([CH3:15])[N:10]=2)=[N:4][CH:5]=[C:6]([Cl:8])[CH:7]=1.C(=O)([O-])[O-].[K+].[K+].CN(C)C=O.Cl[CH:28]([F:30])[F:29]>CCCCCC.C(OCC)(=O)C>[F:1][C:2]1[C:3]([C:9]2[CH:13]=[C:12]([O:14][CH:28]([F:30])[F:29])[N:11]([CH3:15])[N:10]=2)=[N:4][CH:5]=[C:6]([Cl:8])[CH:7]=1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 6372ChlorodifluoromethaneHCID 11430Potassium CarbonateHCID 178481771HCID 178481771, compound

Product 1

HCID 217121323-(3-fluoro-5chloro-2-pyridyl)-5-difluoromethoxy-1-methyl-[1H]-pyrazole

Reagents, catalysts & solvents 1

HCID 21226206Ethyl acetate hexaneSolvent

Conditions

Temperature
85 °C

Procedure

46.0 g of 3-(3-fluoro-5-chloro-2-pyridyl)-5-hydroxy-1-methyl-[1H]-pyrazole (Example P13) and 84 g of potassium carbonate are introduced into 250 ml of dry dimethylformamide and heated to 85° C. While stirring well, Freon 22 (chlorodifluoromethane) is then introduced for a period of 2 hours. TLC analysis of a worked-up sample (silica gel 60 F2s; eluant: n-hexane/ethyl acetate/glacial acetic acid 20/20/1, UV) shows that there is no starting material present. The reaction mixture is partitioned between water and diethyl ether (foaming occurs on the addition of water). After extraction by shaking, and separation of the phases, the ethereal phase is washed twice with water and once with brine. After drying the organic phase over sodium sulfate and filtration, concentration in vacuo is carried out and the residue is purified by means of flash chromatography (silica gel; eluant: n-hexane/ethyl acetate 2/1 (v/v)). 22.0 g of the desired title compound are obtained in the form of a light-yellow solid.

Workup

  1. customThe reaction mixture is partitioned between water and diethyl ether (foaming
  2. additionoccurs on the addition of water)
  3. extractionAfter extraction
  4. stirringby shaking
  5. customseparation of the phases
  6. washthe ethereal phase is washed twice with water and once with brine
  7. customAfter drying the organic phase
  8. filtrationover sodium sulfate and filtration, concentration in vacuo
  9. customthe residue is purified by means of flash chromatography (silica gel; eluant: n-hexane/ethyl acetate 2/1 (v/v))

Sources & evidence

ORD record
ord-2080b9f32918474497039ae9c8b78324
Source dataset
uspto-grants-2001_08
Patent number
US06274536B1

Reaction notes

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