3-Cyanopyridine → HCID 23320889, compound

HRID 280604Notes

Reaction equation

HRID 280604 reaction equation
C([Li])CCC.Br[C:7]1[S:11][C:10]2[CH:12]=[C:13]([Br:16])[CH:14]=[CH:15][C:9]=2[C:8]=1[CH3:17].[C:18]([C:20]1[CH:21]=[N:22][CH:23]=[CH:24][CH:25]=1)#N.Cl.[OH-:27].[Na+]>CCCCCC.CCOCC>[N:22]1[CH:23]=[CH:24][CH:25]=[C:20]([C:18]([C:7]2[S:11][C:10]3[CH:12]=[C:13]([Br:16])[CH:14]=[CH:15][C:9]=3[C:8]=2[CH3:17])=[O:27])[CH:21]=1

Participants

8

Reactant 5

HCID 793-CyanopyridineHCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 13540105HCID 13540105, compoundHCID 178418339Butyllithium

Product 1

HCID 23320889HCID 23320889, compound

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent2×HCID 8058HexaneSolvent

Procedure

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°.

Workup

  1. stirringThe resulting mixture was stirred at -70° for 3 hours
  2. waitat room temperature for a further 2 hours
  3. stirringwith stirring
  4. customthe layers were separated
  5. extractionThe ether layer was extracted with concentrated hydrochloric acid (20 ml)
  6. temperaturewarmed
  7. customhydrolysis of the intermediate ketimine salt
  8. temperatureThe solution was cooled
  9. extractionThe mixture was extracted several times with ethyl acetate
  10. washthe combined extracts were washed with water
  11. dry with materialdried (Na2SO4)
  12. customEvaporation of the solvent
  13. customgave a solid which
  14. customwas chromatographed on silica gel
  15. washElution with chloroform/petrol (b.p. 40°-60°) (2:1)
  16. customgave a solid which
  17. customwas crystallised from ethyl acetate/petrol (b.p. 40°-60°)

Sources & evidence

ORD record
ord-7150322af9654bc49f6703df6c4619ef
Source dataset
uspto-grants-1986_05
Patent number
US04590200

Reaction notes

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