Reaktion #509278

Reaktionsgleichung

iodine

2,2-dimethyl-N-pyridin-3-yl-propionamide

tetramethylene diamine

NH4Cl

n-butyllithium

→

title compound

Ausbeute 23.3%

N-(4-Iodo-pyridin-3-yl)-2,2-dimethyl-propionamide

Ausbeute 23.3%

Lösungsmittel

diethyl ether

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeEquip a 250 mL 3-neck round bottom flask with: a magnetic stirrer
2. 2
   TemperaturCool
3. 3
   Sonstigethe reaction to −78° C
4. 4
   Sonstigethe reaction
5. 5
   TemperaturCool
6. 6
   Sonstigethe reaction to −78° C
7. 7
   Sonstigeto the reaction via the addition funnel
8. 8
   workup.ADDITIONmix 2.5 hours at −68° C
9. 9
   SonstigeQuench
10. 10
    Sonstigethe reaction
11. 11
    ExtraktionExtract with ethyl acetate (100 mL)
12. 12
    WaschenWash the organic layer with a saturated aqueous sodium thiosulfate solution (100 mL) and saturated aqueous sodium chloride
13. 13
    TrocknenDry the organic phase over sodium sulfate
14. 14
    Filtrationfilter
15. 15
    EinengenConcentrate in vacuo
16. 16
    Sonstigeto give brown oil
17. 17
    WaschenChromatograph on silica (80 g) eluting with a gradient of 100% dichloromethane to 70% ethyl acetate/30% dichloromethane

Vorschrift

Equip a 250 mL 3-neck round bottom flask with: a magnetic stirrer, a thermocouple, a dry ice/acetone bath, a nitrogen atmosphere, and an addition funnel. Charge 2,2-dimethyl-N-pyridin-3-yl-propionamide (3.0 g, 16.8 mmol), diethyl ether (67 mL), tetramethylene diamine (4.68 g, 6.08 mL, 40.3 mmol). Cool the reaction to −78° C. Add slowly via glass syringe n-butyllithium (2.5 M solution in hexane, 16.2 mL, 40.3 mmol) over 10 min. Allow the reaction to warm to −13° C. over 2 hours. Cool the reaction to −78° C. Add an iodine solution (8.5 g, 33.6 mmol in 20 mL THF) to the reaction via the addition funnel and mix 2.5 hours at −68° C. Quench the reaction by the addition of saturated aqueous NH4Cl solution (40 mL). Extract with ethyl acetate (100 mL) and discard the aqueous phase. Wash the organic layer with a saturated aqueous sodium thiosulfate solution (100 mL) and saturated aqueous sodium chloride. Dry the organic phase over sodium sulfate and filter. Concentrate in vacuo to give brown oil. Chromatograph on silica (80 g) eluting with a gradient of 100% dichloromethane to 70% ethyl acetate/30% dichloromethane to afford the title compound (1.19 g, 23%). MS (ES) m/z 305 [M+1]+

Quelle