反応 #706797

ord-b86d58c6df5441589df6945e10a4a6e9

反応条件

温度
0°CELSIUS
詳細条件
See reaction.notes.procedure_details.

後処理

  1. 1
    温度The resulting solution was warmed to room temperature
  2. 2
    温度This solution was heated to 50° C. for 2 hours
  3. 3
    温度cooled to room temperature
  4. 4
    その他the reaction quenched by the addition of saturated aqueous NH4Cl
  5. 5
    抽出Thei solution was extracted with EtOAc
  6. 6
    洗浄the combined organic layers washed with H2O and saturated aqueous NaCl
  7. 7
    乾燥before being dried (MgSO4)
  8. 8
    濃縮concentrated under reduced pressure

実験手順

A solution of 2-methylthiophene (130.0 mg, 1.30 mmol) in 2.0 mL of THF was cooled to -78° C. and n-butyllithium (83.3 mg, 1.30 mmol, 0.84 ml of a 1.6M solution in hexanes) was added and the solution warmed to 0° C. during 1.5 hours. A solution of ZnCl2 (341.0 mg, 2.50 mmol) in 3.0 mL THF was slowly added via cannula. The resulting solution was warmed to room temperature, stirred for 40 minutes, and transferred via cannula to a solution of ethyl 4-[(2,2-dimethyl-4-trifluoromethanesulfonyloxy-7-fluoro-(2H)-thiochromen-6-yl)ethynyl]-benzoate (Compound 211, 158.0 mg, 0.31 mmol) and tetrakis(triphenylphosphine) palladium(0) (24.0 mg, 0.02 mmol) in 2.0 mL THF. This solution was heated to 50° C. for 2 hours, cooled to room temperature, and the reaction quenched by the addition of saturated aqueous NH4Cl. Thei solution was extracted with EtOAc and the combined organic layers washed with H2O and saturated aqueous NaCl before being dried (MgSO4) and concentrated under reduced pressure. The title compound, 70.0 mg (50%), was isolated by column chromatography (3% EtOAc/hexanes) as a waxy solid. 1H NMR (300 MHz, CDCl3) δ:8.01 (2H, d, J=8.3 Hz), 7.61 (1H, d, J=7.5 Hz), 7.58 (2H, d, J=8.3 Hz), 7.13 (1H, d, J=7.2 Hz), 6.82 (1H, d, J=4.4 Hz), 6.73 1H, d, J=4.4 Hz), 5.96 (1H, s), 4.39 (2H, q, J=7.1 Hz), 2.52 (3H, s), 1.46 (6H, s), 1.41 (3H, t, J=7.1 Hz).

出典

DOI: 10.6084/m9.figshare.5104873.v1特許: US05958954uspto-grants-1999_09