反应详情

温度

80 °C

A 100 mL, 3-neck round bottom flask was charged with 3-(3-chloro-4,5-dihydro-1H-pyrazol-1-yl)pyridine (3.0 g) and N,N-dimethylformamide (15 mL). potassium persulfate (6.70 g, 24.8 mmol) was added and the reaction was heated to 80° C. for 3 hours. An exotherm at about 110° C. was observed. It was allowed to cool to 80° C. and stirred at 80° C. for 3 hours, at which point a sample was diluted with water and basified with 50 wt % sodium hydroxide solution and extracted with ethyl acetate. The organic layer was analyzed by thin layer chromatography [Eluent: ethyl acetate], which showed that the desired product was formed as the major product, along with a trace of starting material and some minor impurities. The reaction mixture was cooled to 20° C. and diluted with water (50 mL). It was basified with 50% sodium hydroxide and extracted with ethyl acetate (4×30 mL). The organic layers were combined, concentrated to dryness, and purified by flash column chromatography using 30% ethyl acetate/hexanes as eluent. The pure fractions were concentrated to dryness to afford a white solid (1.60 g, 54%): mp 104-106° C.; 1H NMR (400 MHz, CDCl3) δ 8.93 (d, J=27 Hz, 1H), 8.57 (dd, J=4.8, 1.4 Hz, 1H), 8.02 (ddd, J=8.3, 2.7, 1.5 Hz, 1H), 7.91 (d, J=2.6 Hz, 1H), 7.47-7.34 (M, 1H), 6.45 (d, J=2.6 Hz, 1H); 13C NMR (101 MHz, CDCl3) δ 148.01, 142.72, 140.12, 135.99, 128.64, 126.41, 124.01, 108.08; EIMS m/z 179 ([M]+).

1. customat about 110° C.
2. temperatureto cool to 80° C.
3. extractionextracted with ethyl acetate
4. customwas formed as the major product, along with a trace of starting material
5. temperatureThe reaction mixture was cooled to 20° C.
6. extractionextracted with ethyl acetate (4×30 mL)
7. concentrationconcentrated to dryness
8. custompurified by flash column chromatography
9. concentrationThe pure fractions were concentrated to dryness