Reacción #509278

Ecuación de reacción

iodine

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

tetramethylene diamine

NH4Cl

n-butyllithium

→

title compound

Rendimiento 23.3%

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

Rendimiento 23.3%

Disolventes

diethyl ether

Condiciones de reacción

Tratamiento posterior

1. 1
   OtroEquip a 250 mL 3-neck round bottom flask with: a magnetic stirrer
2. 2
   TemperaturaCool
3. 3
   Otrothe reaction to −78° C
4. 4
   Otrothe reaction
5. 5
   TemperaturaCool
6. 6
   Otrothe reaction to −78° C
7. 7
   Otroto the reaction via the addition funnel
8. 8
   workup.ADDITIONmix 2.5 hours at −68° C
9. 9
   OtroQuench
10. 10
    Otrothe reaction
11. 11
    ExtracciónExtract with ethyl acetate (100 mL)
12. 12
    LavadoWash the organic layer with a saturated aqueous sodium thiosulfate solution (100 mL) and saturated aqueous sodium chloride
13. 13
    SecadoDry the organic phase over sodium sulfate
14. 14
    Filtraciónfilter
15. 15
    ConcentraciónConcentrate in vacuo
16. 16
    Otroto give brown oil
17. 17
    LavadoChromatograph on silica (80 g) eluting with a gradient of 100% dichloromethane to 70% ethyl acetate/30% dichloromethane

Procedimiento

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]+

Fuente