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

HRID 1615500ノート

反応式

HRID 1615500 の反応式
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

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

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

反応条件

温度
90 °C

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-8bc7fa53ee1e439f9f3b0ef02ad18e0d
出典データセット
uspto-grants-2014_07
特許番号
US08765746B2

反応ノート

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