반응 #313186

반응 방정식

magnesium

3-bromopentane

2,2-dimethyl-N-(6-methyl-pyridazine-3-yl)-propionamide

sodium tartrate

iodine

bromopentane

magnesium

→

title compound

N-[4-(1-Ethyl-propyl)-6-methyl-pyridazin-3-yl]-2,2-dimethyl-propionamide

용매

diethyl ether

ethyl acetate

tetrahydrofuran

반응 조건

후처리

1. 1
   기타To a dry 3 L flask fitted with a condensor and drop funnel
2. 2
   온도Heat gun
3. 3
   기타dry the entire apparatus under vacuum
4. 4
   온도to cool
5. 5
   workup.ADDITIONadd enough ether
6. 6
   기타until bubbling
7. 7
   workup.STIRRINGStir 30 minutes longer
8. 8
   기타after bubbling ceases
9. 9
   workup.STIRRINGStir 1 h
10. 10
    workup.STIRRINGstir 30 minutes
11. 11
    workup.STIRRINGstir 1 h
12. 12
    추출Separate layers and extract aqueous several times with ethyl acetate
13. 13
    기타Combine organic layers and evaporate solvents
14. 14
    workup.STIRRINGstir 2 h
15. 15
    세척Wash the organic phase once with aqueous solution of sodium sulfite
16. 16
    건조Dry over sodium sulfate
17. 17
    여과filter
18. 18
    기타evaporate to red oil
19. 19
    기타Combine product fractions, evaporate
20. 20
    기타triturate residue in ethyl acetate
21. 21
    여과filter

실험 절차

To a dry 3 L flask fitted with a condensor and drop funnel is added 19.2 g (0.792 moles) of activated magnesium powder. Heat gun dry the entire apparatus under vacuum, allow to cool, add enough ether to cover the magnesium. To the addition funnel is added 100 g (0.662 mmol) of 3-bromopentane in 175 ml of diethyl ether. Add ⅓ of the bromopentane solution to the magnesium and stir under nitrogen until bubbling occurs, then drip in the rest at such a rate so that the bubbling continues gently. Stir 30 minutes longer after bubbling ceases. Next, drip in 21.3 g (0.110 mmol) of 2,2-dimethyl-N-(6-methyl-pyridazine-3-yl)-propionamide dissolved in 225 ml dry tetrahydrofuran. Stir 1 h. Carefully add over 1 L of saturated sodium tartrate and stir 30 minutes. Transfer to larger flask and add 2 L of ethyl acetate and stir 1 h. Separate layers and extract aqueous several times with ethyl acetate. Combine organic layers and evaporate solvents. Take up in 600 ml of methylene chloride and add 28 g (0.110 mol) of iodine and stir 2 h. Wash the organic phase once with aqueous solution of sodium sulfite then water. Dry over sodium sulfate, filter and evaporate to red oil. Chromatograph using 6:1 hexanes:ethyl acetate to 100% ethyl acetate. Combine product fractions, evaporate, and triturate residue in ethyl acetate and filter to obtain 12.0 g (45.6 mmol, 41.4%) of the title compound as a light tan solid. 1H-NMR (DMSO-d6): δ 9.88 (s, 1H); 7.59 (s, 1H); 2.60 (s, 3H); 2.39-2.42 (m, 1H); 1.21-1.37 (m, 2H); 1.38-1.43 (m, 2H); 1.23 (s, 9H); 0.71 (t, J=7.49 Hz, 6H) ppm. MS/ES+=264.

출처