반응 #47445

ord-b771612cc67d44dfa8803230e4435e56

반응 조건

온도
130°CELSIUS
상세 조건
See reaction.notes.procedure_details.

후처리

  1. 1
    기타the resulting mixture was sparged with nitrogen
  2. 2
    기타transferred to an Emry Optimizer microwave reaction vessel
  3. 3
    기타dilute hydrochloric acid and separated
  4. 4
    세척The organic phase was washed with a saturated sodium bicarbonate solution
  5. 5
    건조a saturated sodium chloride solution and dried over sodium sulfate
  6. 6
    여과The mixture was filtered
  7. 7
    기타evaporated
  8. 8
    기타the residue purified by ISCO flash chromatography (Teledyne Isco RediSep Flash Column 80 g, 0% to 50% ethyl acetate/hexanes) which

실험 절차

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.

출처

DOI: 10.6084/m9.figshare.5104873.v1특허: US07741327B2uspto-grants-2010_06