Dichloromethane → HCID 22326934, compound

HRID 1454319Notes

Reaction equation

HRID 1454319 reaction equation
Br[C:2]1[C:7]2[S:8][CH:9]=[CH:10][C:6]=2[CH:5]=[CH:4][CH:3]=1.[N:11]1[CH:16]=[CH:15][C:14](B(O)O)=[CH:13][CH:12]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].C(Cl)Cl>Cl[Pd]Cl.O.O1CCOCC1>[S:8]1[CH:9]=[CH:10][C:6]2[CH:5]=[CH:4][CH:3]=[C:2]([C:14]3[CH:15]=[CH:16][N:11]=[CH:12][CH:13]=3)[C:7]1=2

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 62657Potassium Phosphate, Tribasic2×HCID 2734379(Pyridin-4-yl)boronic acidHCID 120455387-Bromobenzo[b]thiophene

Product 1

HCID 22326934HCID 22326934, compoundYield 129%

Reagents, catalysts & solvents 3

HCID 24290Palladium ChlorideCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To 7-bromo--benzo[b]thiophene (5.28 g, 24.7 mmol) was added pyridine-4-boronic acid (2.734 g, 22.24 mmol), K3PO4 (12.0 g, 56.5 mmol), 37.5 mL of 1,4-dioxane and 3.8 mL of water. The mixture was placed under vacuum for several minutes and flushed with nitrogen. This was repeated 5 times. Pd(dppf)Cl2.CH2Cl2 (0.909 g, 1.11 mmol), PdCl2 (0.1994 g, 1.124 mmol) and 1,1″-bis(diphenylphosphino)ferrocene (0.6234 g, 1.124 mmol) were purged in the same way using high vacuum. The catalyst was added to the reaction flask, which was purged again 3 times. The mixture was stirred at 80° C. under nitrogen. After 1 day TLC showed much starting material remained. Additional K3PO4 (2.3 g, 10.8 mmol) was added after purging. Stirring at 80° C. under nitrogen was continued for 12 to 14 hours and then at room temperature till the next day. The mixture was partitioned between water and ethyl acetate, filtered through Celite and the layers separated. The organic layer was concentrated in vacuum. The residue was redissolved in ethyl acetate, washed with water and dried over magnesium sulfate. Concentration in vacuum gave 6.06 g of dark oil. This was eluted from silica gel with a gradient of hexane and ethyl acetate to give 2.43 g of the title compound as a tan oil that crystallizes slowly, (m.p.71-72° C.).

Workup

  1. waitThe mixture was placed under vacuum for several minutes
  2. customflushed with nitrogen
  3. additionThe catalyst was added to the reaction flask, which
  4. customwas purged again 3 times
  5. customafter purging
  6. stirringStirring at 80° C. under nitrogen
  7. waitwas continued for 12 to 14 hours
  8. customat room temperature
  9. customThe mixture was partitioned between water and ethyl acetate
  10. filtrationfiltered through Celite
  11. customthe layers separated
  12. concentrationThe organic layer was concentrated in vacuum
  13. dissolutionThe residue was redissolved in ethyl acetate
  14. washwashed with water
  15. dry with materialdried over magnesium sulfate
  16. concentrationConcentration in vacuum

Sources & evidence

ORD record
ord-8cacee67849d4ed988c62bb063c77e03
Source dataset
uspto-grants-2009_01
Patent number
US07479500B2

Reaction notes

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