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

HRID 8506

反応式

HRID 8506 の反応式
[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

参加物

7

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 24458Ferrous Chloride触媒HCID 80711,2-Dimethoxyethane溶媒2 回

実験手順

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-α]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).

後処理

  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)

出典と根拠

ORDレコード
ord-0dd7b29960b94ef1aaca212f5b05d9dd
出典データセット
uspto-grants-2006_08
特許番号
US07087618B2

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