反応 #42350

ord-13f72cbfbaea442d8cdb7ad596d52041

反応条件

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

後処理

  1. 1
    その他without further purification
  2. 2
    その他in the following reaction
  3. 3
    温度The reaction mixture is heated
  4. 4
    温度at reflux for 3 h
  5. 5
    温度The reaction mixture is cooled
  6. 6
    ろ過filtered
  7. 7
    洗浄washed with saturated sodium bicarbonate, water, and brine
  8. 8
    乾燥dried (sodium sulfate)
  9. 9
    ろ過filtered
  10. 10
    濃縮concentrated under reduced pressure
  11. 11
    その他Purification by flash column chromatography (silica gel, 60% ethyl acetate/hexane)

実験手順

3-[(Dipropylamino)carbonyl]-5-iodobenzoic acid (12 g, 32 mmol) is dissolved in 20% methanol/benzene (480 mL), and 2M trimethylsilyldiazomethane in hexane (19 mL, 38 mmol) is added slowly. Upon completion of the addition, the solution is concentrated under reduced pressure to give methyl 3-[(dipropylamino)carbonyl]-5-iodobenzoate for use without further purification in the following reaction. To a −70° C. stirred solution of oxazole (120 mg, 1.7 mmol) in tetrahydrofuran (4 mL) is added n-butyllithium (1.6 M in hexanes, 1.2 mL, 1.9 mmol). After 30 min, zinc chloride (1 M in diethyl ether, 5.2 mL, 5.2 mmol) is added and the reaction mixture is warmed to 0° C. for 1 h. To this mixture is added a solution of methyl 3-[(dipropylamino)carbonyl]-5-iodobenzoate (643 mg, 1.6 mmol) in anhydrous tetrahydrofuran (3 mL) followed by palladium(0)tetrakis(triphenylphosphine) (80 mg, 0.07 mmol). The reaction mixture is heated at reflux for 3 h. The reaction mixture is cooled, diluted with ethyl acetate, filtered, washed with saturated sodium bicarbonate, water, and brine, dried (sodium sulfate), filtered, and concentrated under reduced pressure. Purification by flash column chromatography (silica gel, 60% ethyl acetate/hexane) provides the title compound in pure form. 1H NMR (400 MHz, CDCl3) δ 8.77 (s, 1H), 8.27 (s, 1H), 8.14 (s, 1H), 7.80 (s, 1H) 7.32 (s, 1H), 3.52 (t, 2H), 3.22 (t, 2H), 1.75 (m, 2H), 1.30 (m, 2H), 0.97 (t, 3H), 0.79 (t, 3H).

出典

DOI: 10.6084/m9.figshare.5104873.v1特許: US07727997B2uspto-grants-2010_06