반응 #599902

반응 방정식

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

용매

tetrahydrofuran

반응 조건

후처리

1. 1
   workup.WAITThe reaction was analyzed after 3 hours
2. 2
   workup.WAITto have gone to 81% completion, after 24 hours
3. 3
   온도to cool to ambient temperature
4. 4
   기타quenched 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
   기타The layers were separated
7. 7
   추출the aqueous layer was extracted with ethyl acetate (2×30 mL)
8. 8
   workup.ADDITIONsilica gel (37 g) was added
9. 9
   기타The solvent was removed in vacuo
10. 10
    기타to give a solid
11. 11
    기타that was purified
12. 12
    기타to give
13. 13
    농축after concentration

실험 절차

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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