Water → 2-(2-Chloro-4-fluorophenyl)-6-(trifluoromethyl)pyrazolo[1,5-A]pyridine

HRID 354250Notes

Reaction equation

HRID 354250 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9](=[N:21]O)[CH2:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][N:12]=1.C(OC(C(F)(F)F)=O)(C(F)(F)F)=O.C(N(CC)CC)C.O>COCCOC.[Fe](Cl)Cl>[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[C:9]1[CH:10]=[C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][N:12]2[N:21]=1

Participants

7

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 9845Trifluoroacetic anhydrideHCID 865902141-(2-Chloro-4-fluorophenyl)-2-(5-trifluoromethyl-2-pyridinyl)ethanone oxime

Product 1

HCID 99446912-(2-Chloro-4-fluorophenyl)-6-(trifluoromethyl)pyrazolo[1,5-A]pyridineYield 12%

Reagents, catalysts & solvents 2

HCID 24458Ferrous ChlorideCatalystHCID 80711,2-DimethoxyethaneSolvent

Procedure

To a suspension of 1-(2-chloro-4-fluorophenyl)-2-(5-trifluoromethyl-2-pyridinyl)ethanone oxime (2.65 g, 7.95 mmol) in DME (11 ml) at 5° C. was added TFAA (1.13 ml, 7.95 mmol) and the mixture stirred for 10 minutes. Triethylamine (3.3 ml, 23.85 mmol) was then added dropwise over 15 min. After the addition was complete, the reaction mixture was then warmed to room temperature. After stirring for 1 hour, iron (II) chloride (10 mg) was added and the mixture was then heated to 75° C. for 16 hours then allowed to cool. The mixture was poured into water (100 ml) and extracted with dichloromethane (100 ml). The organic extracts were dried over MgSO4 and concentrated to dryness. This residue was purified by column chromatography on silica gel eluting with diethylether-cyclohexane (1:4). Concentration of the appropriate fractions gave 0.3 g (12%) of the title compound.

Workup

  1. additionAfter the addition
  2. stirringAfter stirring for 1 hour
  3. temperaturethe mixture was then heated to 75° C. for 16 hours
  4. temperatureto cool
  5. extractionextracted with dichloromethane (100 ml)
  6. dry with materialThe organic extracts were dried over MgSO4
  7. concentrationconcentrated to dryness
  8. customThis residue was purified by column chromatography on silica gel eluting with diethylether-cyclohexane (1:4)

Sources & evidence

ORD record
ord-d5234ad8cf204a6781e3af66d171cab0
Source dataset
uspto-grants-2004_06
Patent number
US06756498B2

Reaction notes

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