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

HRID 1796545Notes

Reaction equation

HRID 1796545 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][N:5]=[C:4]([CH2:8][C:9]([C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)=[N:10]O)[CH:3]=1.FC(F)(F)C(OC(=O)C(F)(F)F)=O.C(N(CC)CC)C.O>COCCOC.[Fe](Cl)Cl>[Cl:1][C:2]1[CH:7]=[CH:6][N:5]2[N:10]=[C:9]([C:12]3[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=3)[CH:8]=[C:4]2[CH:3]=1

Participants

7

Reactant 4

HCID 962WaterHCID 8471TriethylamineHCID 9845Trifluoroacetic anhydrideHCID 738517532-(4-Chloro-2-pyridinyl)-1-(4-fluorophenyl)ethanone oxime

Product 1

HCID 221748455-Chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridineYield 57%

Reagents, catalysts & solvents 2

HCID 24458Ferrous ChlorideCatalystHCID 80711,2-DimethoxyethaneSolvent2×

Procedure

To a solution of 2-(4-chloro-2-pyridinyl)-1-(4-fluorophenyl)ethanone oxime (8.0 g, 30 mmol) in 1,2-dimethoxyethane (50 mL) at 0° C. was added trifluoroacetic anhydride (6.3 g, 30 mmol), keeping the temperature below 10° C. during the addition. After the addition was complete, the reaction was warmed to room temperature. The solution was then cooled to 4° C. and a solution of triethylamine (8.4 mL, 60 mmol) in 1,2-dimethoxyethane (20 mL) was added over a period of 0.5 hours. The mixture was allowed to warm to room temperature and was stirred for 1.5 hours. To this mixture was added iron(II) chloride (40 mg) and the reaction was heated at 75° C. for 15 hours. The reaction mixture was poured into water (300 mL). The resulting suspension was extracted with ethyl acetate. The combined organics were dried (magnesium sulfate), filtered and concentrated to a solid residue. This residue was purified by flash chromatography (1:1 ethyl acetate-hexane) to give 5-chloro-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridine (4.2 g, 57%) as a white solid. 1H NMR (CDCl3): δ 8.36 (d, 1H), 7.93 (q, 2H), 7.49 (d, 1H), 7.15 (t, 2H), 6.70 (dd, 1H), 6.69 (s, 1H). 19F NMR (CDCl3): δ −113.30; MS m/z 247 (M+1).

Workup

  1. customthe temperature below 10° C.
  2. additionduring the addition
  3. additionAfter the addition
  4. temperatureThe solution was then cooled to 4° C.
  5. temperatureto warm to room temperature
  6. temperaturethe reaction was heated at 75° C. for 15 hours
  7. extractionThe resulting suspension was extracted with ethyl acetate
  8. dry with materialThe combined organics were dried (magnesium sulfate)
  9. filtrationfiltered
  10. concentrationconcentrated to a solid residue
  11. customThis residue was purified by flash chromatography (1:1 ethyl acetate-hexane)

Sources & evidence

ORD record
ord-d0260ac914da46edb89395b9ac74102f
Source dataset
uspto-grants-2006_04
Patent number
US07030134B2

Reaction notes

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