Tetrahydrofuran → 1-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-carbonyl Chloride

HRID 924613

Reaction equation

HRID 924613 reaction equation
[Cl:1][C:2]1[C:3]([N:8]2[CH:12]=[CH:11][C:10]([C:13]([F:16])([F:15])[F:14])=[N:9]2)=[N:4][CH:5]=[CH:6][CH:7]=1.C([Mg][Cl:21])(C)C.[O:22]1[CH2:26]CCC1>>[Cl:1][C:2]1[C:3]([N:8]2[C:12]([C:26]([Cl:21])=[O:22])=[CH:11][C:10]([C:13]([F:16])([F:14])[F:15])=[N:9]2)=[N:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 3

HCID 8028Tetrahydrofuran2×HCID 179762913-chloro-2-(3-(trifluoromethyl)-1H-pyrazol-1-yl)pyridineHCID 178418918HCID 178418918, compound

Product 1

HCID 184469281-(3-chloro-2-pyridinyl)-3-(trifluoromethyl)-1H-pyrazole-5-carbonyl ChlorideYield 84.6%

Conditions

Temperature
-5 °C

Procedure

In a reaction vessel equipped with a thermometer, septum, nitrogen inlet and stirring bar, 500 mg (2.02 mmol) of 1-(3-chloro-2-pyridyl)-3-trifloromethyl-1H-pyrazole were dissolved in 3 ml of dry tetrahydrofuran. By means of a syringe, 2.0 ml of a 2 M solution of isopropyl magnesium chloride in tetrahydrofuran were added dropwise with stirring, while cooling the vessel with an ice bath and keeping the internal temperature at about 20° C. The ice bath was removed and the mixture was stirred for further 20 minutes at 23° C. Then the mixture was cooled again to −5° C. and 4.25 ml of a 20% (w/w) solution of phosgene in toluene were added dropwise with stirring. The mixture was allowed to war at 23° C. and stirred for further 1 h at 23° C. The thus obtained reaction mixture was evaporated to dryness, redissolved in toluene and stirred for further 30 min. at 50° C. Solids were removed by filtration and washed with toluene. The combined filtrates were evaporated to dryness to yield 0.53 g of the title compound with a purity >85% (yield 84.6%).

Workup

  1. customIn a reaction vessel equipped with a thermometer, septum, nitrogen inlet
  2. stirringwith stirring
  3. temperaturewhile cooling the vessel with an ice bath
  4. customat about 20° C
  5. customThe ice bath was removed
  6. stirringthe mixture was stirred for further 20 minutes at 23° C
  7. addition4.25 ml of a 20% (w/w) solution of phosgene in toluene were added dropwise
  8. stirringwith stirring
  9. customwas allowed to war at 23° C.
  10. stirringstirred for further 1 h at 23° C
  11. customThe thus obtained reaction mixture
  12. customwas evaporated to dryness
  13. dissolutionredissolved in toluene
  14. stirringstirred for further 30 min. at 50° C
  15. customSolids were removed by filtration
  16. washwashed with toluene
  17. customThe combined filtrates were evaporated to dryness

Sources & evidence

ORD record
ord-d18ce0b8da7243d4be596d7660e86b7b
Source dataset
uspto-grants-2016_03
Patent number
US09282741B2

Linked notes

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