反应 #8602

反应方程式

water

triethylamine

2-(4-chloro-2-pyridinyl)-1-(4-fluorophenyl)ethanone oxime

trifluoroacetic anhydride

→

5-chloro-2-(4-fluorophenyl)pyrazolo[1,5-α]pyridine

收率 57.0%

溶剂

1,2-dimethoxyethane

1,2-dimethoxyethane

反应条件

后处理

1. 1
   其他the temperature below 10° C.
2. 2
   workup.ADDITIONduring the addition
3. 3
   workup.ADDITIONAfter the addition
4. 4
   温度The solution was then cooled to 4° C.
5. 5
   温度to warm to room temperature
6. 6
   温度the reaction was heated at 75° C. for 15 hours
7. 7
   萃取The resulting suspension was extracted with ethyl acetate
8. 8
   干燥The combined organics were dried (magnesium sulfate)
9. 9
   过滤filtered
10. 10
    浓缩concentrated to a solid residue
11. 11
    其他This residue was purified by flash chromatography (1:1 ethyl acetate-hexane)

实验过程

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).

来源