تفاعل #8602

معادلة التفاعل

water

triethylamine

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

trifluoroacetic anhydride

→

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

المردود 57.0%

المذيبات

1,2-dimethoxyethane

1,2-dimethoxyethane

ظروف التفاعل

المعالجة

1. 1
   أخرىthe temperature below 10° C.
2. 2
   workup.ADDITIONduring the addition
3. 3
   workup.ADDITIONAfter the addition
4. 4
   درجة الحرارةThe solution was then cooled to 4° C.
5. 5
   درجة الحرارةto warm to room temperature
6. 6
   درجة الحرارةthe reaction was heated at 75° C. for 15 hours
7. 7
   استخلاصThe resulting suspension was extracted with ethyl acetate
8. 8
   تجفيفThe combined organics were dried (magnesium sulfate)
9. 9
   ترشيحfiltered
10. 10
    تركيزconcentrated to a solid residue
11. 11
    أخرىThis residue was purified by flash chromatography (1:1 ethyl acetate-hexane)

الإجراء التجريبي

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).

المصدر