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

HRID 1532569Notes

Reaction equation

HRID 1532569 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 H14) and 84 g of potassium carbonate are initially introduced into 250 ml of dry dimethylformamide and the mixture is heated up to 85° C. Freon 22 (chlorodifluoromethane) is then passed in over a period of 2 hours, with thorough stirring. TLC analysis of a worked-up sample (silica gel 60 F254; n-hexane/ethyl acetate/glacial acetic acid 20/20/1, UV) shows that no further starting material is present. The reaction mixture is partitioned between water and diethyl ether (foaming on addition of water). After extraction by shaking and separation of the phases, the ether phase is washed twice with water and once with brine. After the organic phase has been dried over sodium sulfate and filtered, the filtrate is concentrated in vacuo and the residue is purified by means of flash chromatography (silica gel; eluting agent: n-hexane/ethyl acetate 2/1 (v/v)). 22.0 g of the desired title compound are obtained as a pale yellow solid.

Workup

  1. customis then passed in over a period of 2 hours, with thorough stirring
  2. customThe reaction mixture is partitioned between water and diethyl ether (foaming on addition of water)
  3. extractionAfter extraction
  4. customseparation of the phases
  5. washthe ether phase is washed twice with water and once with brine
  6. dry with materialAfter the organic phase has been dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationthe filtrate is concentrated in vacuo
  9. customthe residue is purified by means of flash chromatography (silica gel; eluting agent: n-hexane/ethyl acetate 2/1 (v/v))

Sources & evidence

ORD record
ord-00a73c92ec95410f8a25cef11d3f05b8
Source dataset
uspto-grants-2001_03
Patent number
US06204221B1

Reaction notes

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