Iodine → N-(4-Iodopyridin-3-yl)-2,2-dimethylpropanamide

Temperatur

-13 °C

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]+

1. customEquip a 250 mL 3-neck round bottom flask with: a magnetic stirrer
2. temperatureCool
3. customthe reaction to −78° C
4. customthe reaction
5. temperatureCool
6. customthe reaction to −78° C
7. customto the reaction via the addition funnel
8. additionmix 2.5 hours at −68° C
9. customQuench
10. customthe reaction
11. extractionExtract with ethyl acetate (100 mL)
12. washWash the organic layer with a saturated aqueous sodium thiosulfate solution (100 mL) and saturated aqueous sodium chloride
13. dry with materialDry the organic phase over sodium sulfate
14. filtrationfilter
15. concentrationConcentrate in vacuo
16. customto give brown oil
17. washChromatograph on silica (80 g) eluting with a gradient of 100% dichloromethane to 70% ethyl acetate/30% dichloromethane

ORD-Eintrag

ord-af6df10f30894d27aab6aed98815b222

Quelldatensatz

uspto-grants-2012_01

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08101628B2