Reaktion #367786

Reaktionsgleichung

hydrochloric acid

n-butyl-lithium

2,6-dibromo-3-methylbenzo[b]thiophene

3-cyanopyridine

sodium hydroxide

→

6-bromo-3-methylbenzo[b]thien-2-yl pyrid-3-yl ketone

Lösungsmittel

hexane

ether

ether

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGThe resulting mixture was stirred at -70° for 3 hours
2. 2
   workup.WAITat room temperature for a further 2 hours
3. 3
   workup.STIRRINGwith stirring
4. 4
   Sonstigethe layers were separated
5. 5
   ExtraktionThe ether layer was extracted with concentrated hydrochloric acid (20 ml)
6. 6
   Temperaturwarmed
7. 7
   Sonstigehydrolysis of the intermediate ketimine salt
8. 8
   TemperaturThe solution was cooled
9. 9
   ExtraktionThe mixture was extracted several times with ethyl acetate
10. 10
    Waschenthe combined extracts were washed with water
11. 11
    Trocknendried (Na2SO4)
12. 12
    SonstigeEvaporation of the solvent
13. 13
    Sonstigegave a solid which
14. 14
    Sonstigewas chromatographed on silica gel
15. 15
    WaschenElution with chloroform/petrol (b.p. 40°-60°) (2:1)
16. 16
    Sonstigegave a solid which
17. 17
    Sonstigewas crystallised from ethyl acetate/petrol (b.p. 40°-60°)

Vorschrift

A solution of n-butyl-lithium in hexane (16.3 ml of 1.55M solution) was added to a stirred solution of 2,6-dibromo-3-methylbenzo[b]thiophene (7.65 g) in dry ether (150 ml) at -70° under dry nitrogen. The mixture was stirred for 30 minutes at -70° and then 3-cyanopyridine (2.60 g) in dry ether (50 ml) was added dropwise over 5 minutes. The resulting mixture was stirred at -70° for 3 hours and then at room temperature for a further 2 hours. Concentrated hydrochloric acid (40 ml) was added dropwise with stirring and the layers were separated. The ether layer was extracted with concentrated hydrochloric acid (20 ml) and the acid extracts were combined and warmed to complete hydrolysis of the intermediate ketimine salt. The solution was cooled and made alkaline with sodium hydroxide solution. The mixture was extracted several times with ethyl acetate and the combined extracts were washed with water and dried (Na2SO4). Evaporation of the solvent gave a solid which was chromatographed on silica gel. Elution with chloroform/petrol (b.p. 40°-60°) (2:1) gave a solid which was crystallised from ethyl acetate/petrol (b.p. 40°-60°) to give 6-bromo-3-methylbenzo[b]thien-2-yl pyrid-3-yl ketone (4.70 g), m.p. 110°-111°.

Quelle