Reaction #53240

Reaction equation

CBr4

butyllithium

N,N-dimethylamine ethanol

4-methoxypyridine

→

4-methoxy-2-bromopyridine

Yield 22.0%

Solvents

water

—

hexanes

Conditions

Workup

1. 1
   workup.WAITcontinued at 0° C. for one hour before the reaction mixture
2. 2
   TemperatureThe reaction temperature was maintained at 0° C. for 2.5 hours
3. 3
   Otherto quench
4. 4
   Otherthe reaction
5. 5
   OtherThe aqueous layer was then separated
6. 6
   Extractionextracted with methylene chloride
7. 7
   ExtractionThe organic extractions
8. 8
   Washwere washed with brine
9. 9
   Dryingdried over magnesium sulfate
10. 10
    Otherevaporated
11. 11
    Otherto give crude product
12. 12
    OtherThe crude product was purified by column chromatography
13. 13
    OtherThe purified product was collected
14. 14
    Concentrationconcentrated

Procedure

A solution of N,N-dimethylamine ethanol (78.086 g, 0.876 mole) in anhydrous hexanes(1241 mL.) was cooled to 0° C. and butyllithium (2M soln. 876 mL., 1.757 mole) was added by use of an addition funnel. After 30 minutes at 0° C., 4-methoxypyridine(47.87 g, 0.438 mole) was added. Stirring continued at 0° C. for one hour before the reaction mixture was cooled to −78° C. and a solution of CBr4 (363 g, 1.093 mole) was added. The reaction temperature was maintained at 0° C. for 2.5 hours. The water was then added to quench the reaction. The aqueous layer was then separated and extracted with methylene chloride. The organic extractions were washed with brine, dried over magnesium sulfate and evaporated to give crude product. The crude product was purified by column chromatography using 80/20 ethyl acetate/hexanes as the eluants. The purified product was collected and concentrated to give 4-methoxy-2-bromopyridine (17 g. 22% yield).

Source