Reaktion #466555

Reaktionsgleichung

iodine

2,2-dimethyl-N-[6-(4-methyl-piperazin-1-yl)-pyridin-3-yl]-propionamide

N,N,N′,N′-tetramethylethylenediamine

sodium thiosulfate pentahydrate

n-butyllithium

dry ice

→

title compound

Ausbeute 42.6%

N-[4-Iodo-6-(4-methyl-piperazin-1-yl)-pyridin-3-yl]-2,2-dimethyl-propionamide

Ausbeute 42.6%

Lösungsmittel

diethyl ether

tetrahydrofuran

tetrahydrofuran

water

hexane

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturAfter cooling again to −78° C.
2. 2
   workup.ADDITIONwere added dropwise during 15 min
3. 3
   Sonstigehad reached 0° C
4. 4
   Sonstigethe organic layer was separated
5. 5
   ExtraktionThe aqueous layer was extracted twice with 500 ml dichloromethane
6. 6
   Trocknenthe combined organic layers were dried (magnesium sulfate)
7. 7
   Sonstigeevaporated

Vorschrift

A solution of 30 g (108 mmol) 2,2-dimethyl-N-[6-(4-methyl-piperazin-1-yl)-pyridin-3-yl]-propionamide and 58 ml (380 mmol) N,N,N′,N′-tetramethylethylenediamine under argon in 650 ml tetrahydrofuran was cooled in a dry ice bath to −78° C. Within lh, 239 ml (380 mmol) of a 1.6 N n-butyllithium solution in hexane were added dropwise. The reaction mixture was allowed to warm up to −30° C. overnight. After cooling again to −78° C., 43.6 g (170 mmol) iodine dissolved in 60 ml tetrahydrofuran were added dropwise during 15 min. The dry ice bath was replaced by an ice bath and a solution of 90 g (363 mmol) sodium thiosulfate pentahydrate in 250 ml water were added within 10 min when the temperature of the reaction mixture had reached 0° C. Then, 1000 ml diethyl ether were added and the organic layer was separated. The aqueous layer was extracted twice with 500 ml dichloromethane and the combined organic layers were dried (magnesium sulfate) and evaporated. Flash chromatography gave 18.5 g (42%) of the title compound as a light brown oil which crystallized upon standing at room temperature.

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