Sodium Iodide → 3-(3-Fluoro-5-chloro-2-pyridyl)-5-(2.2.2-trifluoroethoxy)-1-methyl-[1H]-pyrazole

HRID 1532583Notes

Reaction equation

HRID 1532583 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+].[F:22][C:23]([F:27])([F:26])[CH2:24]O.CC1C=CC(S([O-])(=O)=O)=CC=1.[I-].[Na+]>CN1CCCC1=O>[F:1][C:2]1[C:3]([C:9]2[CH:13]=[C:12]([O:14][CH2:24][C:23]([F:27])([F:26])[F:22])[N:11]([CH3:15])[N:10]=2)=[N:4][CH:5]=[C:6]([Cl:8])[CH:7]=1

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 11430Potassium CarbonateHCID 1317224532,2,2-Trifluoro-ethanol 4-methylbenzenesulfonateHCID 178481771HCID 178481771, compound

Product 1

HCID 599468843-(3-Fluoro-5-chloro-2-pyridyl)-5-(2.2.2-trifluoroethoxy)-1-methyl-[1H]-pyrazoleYield 67.3%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
80 °C

Procedure

3.0 g of 3-(3-fluoro-5-chloro-2-pyridyl)-5-hydroxy-1-methyl-[1H]-pyrazole (Example H14) are initially introduced into 30 ml of N-methylpyrrolidone (NMP) together with 3.64 g of potassium carbonate, and 3.49 g of 2,2,2-trifluoro-ethanol 4-methylbenzenesulfonate are added. 0.3 g of sodium iodide is then added and the mixture is stirred overnight at 80° C. It is then cooled to 22° C. and partitioned between dilute hydrochloric acid and diethyl ether. After extraction by shaking and separation of the phases, the ether phase is washed with brine, filtered and concentrated in vacuo together with twice the amount of silica gel. After application of the silica gel to a flash column, the column is eluted with n-hexane/ethyl acetate 2/1. 2.68 g of the desired title compound are obtained as a yellow solid of melting point 72-73° C.

Workup

  1. additionare added
  2. temperatureIt is then cooled to 22° C.
  3. custompartitioned between dilute hydrochloric acid and diethyl ether
  4. extractionAfter extraction
  5. stirringby shaking
  6. customseparation of the phases
  7. washthe ether phase is washed with brine
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo together with twice the amount of silica gel
  10. washAfter application of the silica gel to a flash column, the column is eluted with n-hexane/ethyl acetate 2/1

Sources & evidence

ORD record
ord-2792366fff0741e3930823657e830fd7
Source dataset
uspto-grants-2001_03
Patent number
US06204221B1

Reaction notes

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