Water → 4-(4-chlorophenyl)-2-(pyridin-4-yl)-4H-cyclopenta[b]thiophen-6(5H)-one

HRID 1615500Notes

Reaction equation

HRID 1615500 reaction equation
Br[C:2]1[S:6][C:5]2[C:7](=[O:17])[CH2:8][CH:9]([C:10]3[CH:15]=[CH:14][C:13]([Cl:16])=[CH:12][CH:11]=3)[C:4]=2[CH:3]=1.[N:18]1[CH:23]=[CH:22][C:21](B(O)O)=[CH:20][CH:19]=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]>[Cl:16][C:13]1[CH:14]=[CH:15][C:10]([CH:9]2[C:4]3[CH:3]=[C:2]([C:21]4[CH:22]=[CH:23][N:18]=[CH:19][CH:20]=4)[S:6][C:5]=3[C:7](=[O:17])[CH2:8]2)=[CH:11][CH:12]=1

Participants

7

Reactant 5

HCID 962WaterHCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 2734379(Pyridin-4-yl)boronic acidHCID 681829442-bromo-4-(4-chlorophenyl)-4H-cyclopenta[b]thiophen-6(5H)-one

Product 1

HCID 569711204-(4-chlorophenyl)-2-(pyridin-4-yl)-4H-cyclopenta[b]thiophen-6(5H)-oneYield 88.5%

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 40 mL vial was added a solution of 2-bromo-4-(4-chlorophenyl)-4,5-dihydro-6H-cyclopenta[b]thiophen-6-one (0.150 g, 0.458 mmol) and pyridine-4-boronic acid (0.105 g, 0.855 mmol) in a solution of 1,4-dioxane (8.000 mL, 102.5 mmol) and water (0.800 mL, 44.4 mmol). Cesium carbonate (0.448 g, 1.374 mmol) was added followed by [1,1′-bis(diphenylphosphino)ferrocene]palladium(II)dichloride (0.045 g, 0.055 mmol). The reaction mixture was 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 (10.0 mL) and extracted with EtOAc (10.0 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 ISCO (12 g cartridge, gradient hexanes to 100% EtOAc over 30 min) to afford the title compound (0.132 g, 84%) as a white solid. LC/MS (AA) ES+ 326, 328. 1H NMR (dmso-d6, 400 MHz): δ 8.65-8.63 (m, 2H), 7.79 (s, 1H). 7.77-7.76 (m, 2H), 7.42-7.40 (m, 2H), 7.30-7.28 (m, 2H), 4.72 (dd, 1H), 3.49 (dd, 1H), 2.81 (dd, 1H).

Workup

  1. temperatureThe reaction was cooled to ambient temperature
  2. customquenched by the addition of a saturated aqueous solution of sodium bicarbonate (10.0 mL)
  3. extractionextracted with EtOAc (10.0 mL×3)
  4. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. dry with materialThe crude material was dry
  8. custompurified
  9. customISCO (12 g cartridge, gradient hexanes to 100% EtOAc over 30 min)

Sources & evidence

ORD record
ord-8bc7fa53ee1e439f9f3b0ef02ad18e0d
Source dataset
uspto-grants-2014_07
Patent number
US08765746B2

Reaction notes

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