Dichloromethane → 4-(5-Chloro-benzo[b]thiophen-3-yl)-pyridine

HRID 495417Notes

Reaction equation

HRID 495417 reaction equation
Br[C:2]1[C:3]2[CH:10]=[C:9]([Cl:11])[CH:8]=[CH:7][C:4]=2[S:5][CH:6]=1.[N:12]1[CH:17]=[CH:16][C:15](B(O)O)=[CH:14][CH:13]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C(Cl)Cl>Cl[Pd]Cl.O.O1CCOCC1>[Cl:11][C:9]1[CH:8]=[CH:7][C:4]2[S:5][CH:6]=[C:2]([C:15]3[CH:16]=[CH:17][N:12]=[CH:13][CH:14]=3)[C:3]=2[CH:10]=1

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 62657Potassium Phosphate, TribasicHCID 2734379(Pyridin-4-yl)boronic acidHCID 142423383-Bromo-5-chlorobenzo[b]thiophene

Product 1

HCID 223269384-(5-Chloro-benzo[b]thiophen-3-yl)-pyridineYield 127.6%

Reagents, catalysts & solvents 3

HCID 24290Palladium ChlorideCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

To 3-bromo-5-chloro-benzo[b]thiophene (9.80 g, 39.6 mmol) was added pyridine-4-boronic acid (4.445 g, 36.2 mmol), K3PO4 (19.5 g, 91.9 mmol), 61 mL of 1,4-dioxane and 6 mL of water. The mixture was placed under house vacuum for several minutes and flushed with nitrogen. This was repeated 5 times. Pd(dppf)Cl2.CH2Cl2 (2.71 g, 3.31 mmol), PdCl2 (0.0563 g, 0.318 mmol) and 1,1″-bis(diphenylphosphino)ferrocene (0.1747 g, 0.3151 mmol) were purged in the same way. The catalyst was added to the reaction flask which was purged with nitrogen 3 more times. The mixture was stirred (stir bar) at 80° C. for 22 hours. TLC showed little change. The mixture was mechanically stirred at 80° C. for 4 hours. The mixture was partitioned between water and ethyl acetate, filtered through Celite and the layers were separated. The organic layer was evaporated. The residue was dissolved in ethyl acetate, washed with water twice. Saturated brine was added the second time to separate the layers more quickly. The organic solution was dried over magnesium sulfate. Filtration and contration in vacuum gave 11.35 g of black oil. This was eluted from silica gel with a gradient of hexane and ethyl acetate to give 3.86 g of recovered starting material and 4.28 g of the title compound as light brown crystals, m.p. 90-91° C.

Workup

  1. waitThe mixture was placed under house vacuum for several minutes
  2. customflushed with nitrogen
  3. additionThe catalyst was added to the reaction flask which
  4. customwas purged with nitrogen 3 more times
  5. stirring(stir bar) at 80° C. for 22 hours
  6. stirringThe mixture was mechanically stirred at 80° C. for 4 hours
  7. customThe mixture was partitioned between water and ethyl acetate
  8. filtrationfiltered through Celite
  9. customthe layers were separated
  10. customThe organic layer was evaporated
  11. dissolutionThe residue was dissolved in ethyl acetate
  12. washwashed with water twice
  13. additionSaturated brine was added the second time
  14. customto separate the layers more quickly
  15. dry with materialThe organic solution was dried over magnesium sulfate
  16. filtrationFiltration and contration in vacuum

Sources & evidence

ORD record
ord-cee34bd5b62c4b3bb8b7af684b163406
Source dataset
uspto-grants-2005_09
Patent number
US06939877B2

Reaction notes

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