Water → HCID 46317398, compound

HRID 1615503Notes

Reaction equation

HRID 1615503 reaction equation
Br[C:2]1[S:3][C:4]([C:7](=[O:9])[CH3:8])=[CH:5][CH:6]=1.[N:10]1[CH:15]=[CH:14][C:13](B(O)O)=[CH:12][CH:11]=1.O1CCOCC1.O.C(=O)([O-])[O-].[Cs+].[Cs+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[N:10]1[CH:15]=[CH:14][C:13]([C:2]2[S:3][C:4]([C:7](=[O:9])[CH3:8])=[CH:5][CH:6]=2)=[CH:12][CH:11]=1

Participants

7

Reactant 5

HCID 962WaterHCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 793352-Acetyl-5-bromothiopheneHCID 2734379(Pyridin-4-yl)boronic acid

Product 1

HCID 46317398HCID 46317398, compoundYield 85.4%

Reagents, catalysts & solvents 1

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)Catalyst

Conditions

Temperature
90 °C

Procedure

To a 100 mL round bottom flask was added a solution of 2-bromo-5-acetylthiophene (0.500 g, 2.438 mmol) and pyridine-4-boronic acid (0.560 g, 4.555 mmol) in a solution of 1,4-dioxane (20.00 mL, 256.3 mmol) and water (4.00 mL, 222 mmol). Cesium carbonate (2.383 g, 7.314 mmol) was added followed by [1,1′-bis(diphenylphosphino)ferrocene]palladium(II)dichloride (0.2407 g, 0.293 mmol). The reaction mixture was fitted with an air condenser and heated to 90° C. and allowed to stir for 18 h. The reaction was cooled to ambient temperature and quenched by the addition of a saturated aqueous solution of sodium bicarbonate (10.00 mL) and extracted with EtOAc (10.00 mL×3). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure The crude material was dry loaded onto silica gel and then purified using a ISCO (24 g cartridge, gradient hexanes to 100% EtOAc over 30 min) to afford the title compound (0.423 g, 81%) as a yellow solid. LC/MS (AA) ES+ 204. 1H NMR (dmso-d6, 400 MHz): δ 8.65-8.64 (m, 2H), 8.02 (d, 1H), 7.92 (d, 1H), 7.76-7.75 (m, 2H), 2.58 (s, 3H).

Workup

  1. customThe reaction mixture was fitted with an air condenser
  2. temperatureThe reaction was cooled to ambient temperature
  3. customquenched by the addition of a saturated aqueous solution of sodium bicarbonate (10.00 mL)
  4. extractionextracted with EtOAc (10.00 mL×3)
  5. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure The crude material
  8. customwas dry
  9. custompurified
  10. customa ISCO (24 g cartridge, gradient hexanes to 100% EtOAc over 30 min)

Sources & evidence

ORD record
ord-81cea63b923e480fae2bfc70a01b1212
Source dataset
uspto-grants-2014_07
Patent number
US08765746B2

Reaction notes

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