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

HRID 1062865Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1062865
[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

Komponenten

7

Edukt 4

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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 24458Ferrous ChlorideKatalysatorHCID 80711,2-DimethoxyethaneLösungsmittel2×

Versuchsvorschrift

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).

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-dc320979bf3b43c48a31264bf8b7497e
Quelldatensatz
uspto-grants-2005_11
Patentnummer
US06962914B2

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