Reaktion #42047

Reaktionsgleichung

hydrochloric acid

magnesium chloride

diethyl malonate

5-bromonicotinoyl chloride

→

objective compound

Ausbeute 24.3%

3-acetyl-5-bromopyridine

Ausbeute 24.3%

Lösungsmittel

toluene

triethylamine

toluene

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONwas added dropwise over 15 minutes
2. 2
   workup.STIRRINGby stirring at room temperature for 2 hours
3. 3
   Sonstigethe aqueous layer was separated
4. 4
   ExtraktionThe aqueous layer was further subjected to extraction with diethyl ether
5. 5
   workup.DISTILLATIONthe solvent was distilled off under reduced pressure
6. 6
   workup.ADDITIONTo the resulting oily product, dimethyl sulfoxide-water (17 ml-0.7 ml) was added
7. 7
   workup.STIRRINGby stirring
8. 8
   Temperaturwith heating at 150 to 160° C. for 2 hours
9. 9
   TemperaturThe reaction solution was air-cooled
10. 10
    workup.ADDITIONwater was added
11. 11
    FiltrationThen, the deposited crystals were collected by filtration
12. 12
    workup.DISSOLUTIONThe deposited crystals were dissolved in ethyl acetate
13. 13
    Waschenwashed in turn with water
14. 14
    Trocknenan aqueous saturated sodium hydrogen carbonate solution and then dried over anhydrous magnesium sulfate
15. 15
    workup.ADDITION0.60 g of activated carbon (Kyoryoku Shirasagi MOIWY433) was added
16. 16
    workup.WAITafter standing for 10 minutes
17. 17
    Sonstigeactivated carbon was removed by filtration
18. 18
    Einengenthe filtrate was concentrated under reduced pressure
19. 19
    SonstigeThe residue was purified by silica gel column chromatography

Vorschrift

1.24 g of ground magnesium chloride was suspended in 13 ml of toluene and 6.2 ml of triethylamine and 2.93 g of diethyl malonate were added in turn. After stirring at room temperature for 1.5 hours, a suspension of 4.08 g of 5-bromonicotinoyl chloride obtained in the step 1 in 10 ml of toluene was added dropwise over 15 minutes, followed by stirring at room temperature for 2 hours. After neutralizing with 40 ml of 1N hydrochloric acid, the aqueous layer was separated. The aqueous layer was further subjected to extraction with diethyl ether and the organic layers were combined, and then the solvent was distilled off under reduced pressure. To the resulting oily product, dimethyl sulfoxide-water (17 ml-0.7 ml) was added, followed by stirring with heating at 150 to 160° C. for 2 hours. The reaction solution was air-cooled, and then water was added. Then, the deposited crystals were collected by filtration. The deposited crystals were dissolved in ethyl acetate, washed in turn with water and an aqueous saturated sodium hydrogen carbonate solution and then dried over anhydrous magnesium sulfate. 0.60 g of activated carbon (Kyoryoku Shirasagi MOIWY433) was added and, after standing for 10 minutes, activated carbon was removed by filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography to obtain 0.89 g of the objective compound as pale yellow crystals.

Quelle