反応 #599902

反応方程式

ethyl bromide

N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)acetamide

sodium tert-butoxide

→

N-(3-Chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)-N-ethylacetamide

溶媒

tetrahydrofuran

反応条件

後処理

1. 1
   workup.WAITThe reaction was analyzed after 3 hours
2. 2
   workup.WAITto have gone to 81% completion, after 24 hours
3. 3
   温度to cool to ambient temperature
4. 4
   その他quenched with ammonium hydroxide/formic acid (HCO2H) buffer (10 mL)
5. 5
   workup.ADDITIONThe mixture was then diluted with tetrahydrofuran (40 mL), ethyl acetate (120 mL), and saturated sodium bicarbonate (30 mL)
6. 6
   その他The layers were separated
7. 7
   抽出the aqueous layer was extracted with ethyl acetate (2×30 mL)
8. 8
   workup.ADDITIONsilica gel (37 g) was added
9. 9
   その他The solvent was removed in vacuo
10. 10
    その他to give a solid
11. 11
    その他that was purified
12. 12
    その他to give
13. 13
    濃縮after concentration

実験手順

In a 125 mL 3-neck round-bottomed flask was added N-(3-chloro-1-(pyridin-3-yl)-1H-pyrazol-4-yl)acetamide (2.57 g, 9.44 mmol), tetrahydrofuran (55 mL), and sodium tert-butoxide (1.81 g, 18.9 mmol). The suspension was stirred for 5 minutes then ethyl bromide (1.41 mL, 18.9 mmol), and tetrabutylammonium iodide (67 mg, 0.2 mmol) were added. The resulting gray colored suspension was then heated to 38° C. The reaction was analyzed after 3 hours and found to have gone to 81% completion, after 24 hours the reaction was found to have gone to completion. The reaction mixture was allowed to cool to ambient temperature and quenched with ammonium hydroxide/formic acid (HCO2H) buffer (10 mL). The mixture was then diluted with tetrahydrofuran (40 mL), ethyl acetate (120 mL), and saturated sodium bicarbonate (30 mL). The layers were separated and the aqueous layer was extracted with ethyl acetate (2×30 mL). The organic layers were combined and silica gel (37 g) was added. The solvent was removed in vacuo to give a solid that was purified using semi-automated silica gel chromatography (RediSep Silica 220 g column; hexanes (0.2% triethylamine)/ethyl acetate, 40/60 to 0/100 gradient elution system, flow rate 150 mL/minutes) to give, after concentration, an orange solid weighing (2.19 g, 88%)

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