Reaktion #58496

Reaktionsgleichung

n-butyl lithium

hexane

2,6-dibromopyridine

1-methyl-N-methyl-N-methoxy-piperidine-4-carboxamide

NaOH

→

2-bromo-6-(1-methylpiperidin-4-ylcarbonyl)-pyridine

Ausbeute 74.0%

Lösungsmittel

dichloromethane

dichloromethane

dichloromethane

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONAfter the addition
2. 2
   Sonstigethe reaction at −78° C. for 1 hr
3. 3
   workup.STIRRINGStir
4. 4
   Sonstigethe reaction at −78° C. for 2 hrs
5. 5
   Temperaturto slowly warm to room temperature overnight
6. 6
   SonstigeQuench
7. 7
   Sonstigethe reaction with 0.1 N NaOH
8. 8
   SonstigeSeparate the organic layer
9. 9
   Trocknendry it over anhydrous sodium sulfate
10. 10
    Sonstigeevaporate the solvent under reduced pressure
11. 11
    SonstigeFurther purify the residue by chromatography on asilica gel column (6%, 2M NH3 in methanol/CH2Cl2 )

Vorschrift

Dissolve 2,6-dibromopyridine (5.5 g, 23.2 mmol) in anhydrous dichloromethane (140 mL) under a nitrogen atmosphere. Cool the reaction mixture to −78° C. Add a solution of n-butyl lithium in hexane (1.6 M, 15.8 mL, 25.3 mmol) very slowly via a syringe. After the addition is complete, stir the reaction at −78° C. for 1 hr. Add a solution of 1-methyl-N-methyl-N-methoxy-piperidine-4-carboxamide (2 g, 11 mmol) in anhydrous dichloromethane (10 mL) dropwise to the reaction mixture. Stir the reaction at −78° C. for 2 hrs, and then allow the mixture to slowly warm to room temperature overnight. Quench the reaction with 0.1 N NaOH. Dilute the solution with dichloromethane (100 mL), transfer into a separatory funnel and shake with 2 N NaOH (50 mL). Separate the organic layer, dry it over anhydrous sodium sulfate, and then evaporate the solvent under reduced pressure. Further purify the residue by chromatography on asilica gel column (6%, 2M NH3 in methanol/CH2Cl2 ) to obtain 2-bromo-6-(1-methylpiperidin-4-ylcarbonyl)-pyridine e (2.3 g, 74% yield). Mass spectrum (ion spray): m/z 283 (M+1).

Quelle