反応 #47445

ord-b771612cc67d44dfa8803230e4435e56

反応条件

温度
130°CELSIUS
詳細条件
See reaction.notes.procedure_details.

後処理

  1. 1
    その他the resulting mixture was sparged with nitrogen
  2. 2
    その他transferred to an Emry Optimizer microwave reaction vessel
  3. 3
    その他dilute hydrochloric acid and separated
  4. 4
    洗浄The organic phase was washed with a saturated sodium bicarbonate solution
  5. 5
    乾燥a saturated sodium chloride solution and dried over sodium sulfate
  6. 6
    ろ過The mixture was filtered
  7. 7
    その他evaporated
  8. 8
    その他the residue purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 80 g, 0% to 50% ethyl acetate/hexanes) which

実験手順

To a mixture of (S)-2-[4-(3-bromo-2-fluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid ethyl ester (prepared as in Example 128, 1.2 g, 2.9 mmol), palladium(II) acetate (0.035 g, 0.15 mmol), tricyclohexylphosphine (0.084 g, 0.30 mmol), and tripotassium phosphate (2.0 g, 9.0 mmol) in toluene (8 mL) was added cyclopropylboronic acid (0.325 g, 3.8 mmol) and water (0.2 mL) and the resulting mixture was sparged with nitrogen and transferred to an Emry Optimizer microwave reaction vessel and heated at 130° C., for 2.5 h. The mixture was taken up in ethyl acetate and dilute hydrochloric acid and separated. The organic phase was washed with a saturated sodium bicarbonate solution, a saturated sodium chloride solution and dried over sodium sulfate. The mixture was filtered and evaporated and the residue purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 80 g, 0% to 50% ethyl acetate/hexanes) which afforded (S)-2-[4-(3-cyclopropyl-2-fluoro-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-4-methyl-pentanoic acid ethyl ester (0.80 g, 74%) as a pale yellow solid.

出典

DOI: 10.6084/m9.figshare.5104873.v1特許: US07741327B2uspto-grants-2010_06