Sulfuric Acid → 5-Amino-1-(6-chloro-1,1,3,3-tetrafluoro-1,3-dihydroisobenzofuran-5-yl)pyrazole

HRID 1871571Notes

Reaction equation

HRID 1871571 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[NH:11][NH2:12])[C:7]([F:14])([F:13])[O:6][C:5]2([F:16])[F:15].Cl[C:18](=[CH2:21])[C:19]#[N:20].S(=O)(=O)(O)O.C(=O)([O-])[O-].[Na+].[Na+]>CO.C(N(CC(O)=O)CC(O)=O)CN(CC([O-])=O)CC([O-])=O.[Na+].[Na+]>[NH2:20][C:19]1[N:11]([C:10]2[CH:9]=[C:8]3[C:4](=[CH:3][C:2]=2[Cl:1])[C:5]([F:16])([F:15])[O:6][C:7]3([F:14])[F:13])[N:12]=[CH:21][CH:18]=1

Participants

7

Reactant 4

HCID 1118Sulfuric AcidHCID 10340Sodium CarbonateHCID 701982-ChloroacrylonitrileHCID 544985185-Chloro-1,1,3,3-tetrafluoro-1,3-dihydroisobenzofuran-6-yl-hydrazine

Product 1

HCID 186915105-Amino-1-(6-chloro-1,1,3,3-tetrafluoro-1,3-dihydroisobenzofuran-5-yl)pyrazoleYield 37.2%

Reagents, catalysts & solvents 2

HCID 13020083Ethylenediaminetetraacetic acid disodium saltCatalystHCID 887MethanolSolvent

Procedure

To a solution wherein 5-chloro-1,1,3,3-tetrafluoro-1,3-dihydroisobenzofuran-6-yl-hydrazine (900 mg, 3.5 mmol) and disodium ethylenediaminetetraacetate (1 mg) are in methanol (6 ml), 2-chloroacrylonitrile (919 mg, 10.5 mmol) was added dropwise at 60° C., and under reflux for 8 hours, subsequently concentrated sulfuric acid (0.5 ml, 9.4 mmol) was added to the solution and was further heated under reflux for 6 hours. After the reaction solution was allowed to cool, anhydrous sodium carbonate (1.17 g, 10.5 mmol) was added to the reaction solution, stirred for 4 hours, and had the solvent distilled off under reduced pressure. Subsequently, water was added to the residue, the solution was extracted with ethyl acetate, and the organic layer was dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure and the residue was subjected to silica gel column chromatography to give 400 mg of 5-amino-1-(6-chloro-1,1,3,3-tetrafluoro-1,3-dihydroisobenzofuran-5-yl)-pyrazole.

Workup

  1. temperatureunder reflux for 8 hours
  2. temperaturewas further heated
  3. temperatureunder reflux for 6 hours
  4. temperatureto cool
  5. distillationdistilled off under reduced pressure
  6. additionSubsequently, water was added to the residue
  7. extractionthe solution was extracted with ethyl acetate
  8. dry with materialthe organic layer was dried over anhydrous magnesium sulfate
  9. distillationThe solvent was distilled off under reduced pressure

Sources & evidence

ORD record
ord-261d8e7013874480ae61c3a4dc14c1e9
Source dataset
uspto-grants-2000_08
Patent number
US06103750

Reaction notes

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