반응 #159083

ord-7793ff03e7b844d2a6a4eeeabfd8788f

반응 조건

온도
80°CELSIUS
상세 조건
See reaction.notes.procedure_details.

후처리

  1. 1
    기타The reaction mixture was flushed with nitrogen
  2. 2
    온도cooled to ambient temperature
  3. 3
    세척Washed with water and brine
  4. 4
    건조dried over Na2SO4
  5. 5
    여과filtered
  6. 6
    농축concentrated in vacuo
  7. 7
    workup.STIRRINGThe mixture was stirred at room temperature for 16 hours
  8. 8
    세척The organic layer was washed with NaHCO3 solution and water
  9. 9
    건조dried over Na2SO4
  10. 10
    여과filtered
  11. 11
    농축concentrated in vacuo
  12. 12
    기타The obtained residue was purified by flash chromatography

실험 절차

Pd(Ph3)4 (37 mg, 0.03 mmol) and PdCl2(Ph3)2 (22 mg, 0.03 mmol) were added to a mixture of pyrrolidine-1,2-dicarboxylic acid 2-[2-(7-bromo-9,10-dihydro-phenanthren-2-yl)-2-oxo-ethyl]ester 1-tert-butyl ester (410 mg, 0.8 mmol) and tributyl(1-ethoxyvinyl)tin (0.32 mL, 0.96 mmol) in 8 mL dioxane. The reaction mixture was flushed with nitrogen, heated at 80° C. for 16 hours, then cooled to ambient temperature. Water (2 mL) and NBS (171 mg, 0.96 mmol) were added and the mixture was stirred at room temperature for 40 minutes, then diluted with ethyl acetate (100 mL). Washed with water and brine, dried over Na2SO4, filtered and concentrated in vacuo. Half of the obtained residue was suspended in acetonitrile (5 mL) To it was added a solution of 2-aza-bicyclo[2.2.1]heptane-2,3-dicarboxylic acid 2-tert-butyl ester (100 mg, 0.41 mmol) and DIPEA (0.068 mL, 0.39 mmol) in 2 mL acetonitrile. The mixture was stirred at room temperature for 16 hours, then diluted with ethyl acetate (100 mL). The organic layer was washed with NaHCO3 solution and water, dried over Na2SO4, filtered and concentrated in vacuo. The obtained residue was purified by flash chromatography to provide the desired product 2-aza-bicyclo[2.2.1]heptane-2,3-dicarboxylic acid 3-(2-{7-[2-(1-tert-butoxycarbonyl-pyrrolidine-2-carbonyloxy)-acetyl]-9,10-dihydro-phenanthren-2-yl}-2-oxo-ethyl) ester 2-tert-butyl ester as a white solid (171 mg, 60% over two steps). m/z 717.2 (M+H)+.

출처

DOI: 10.6084/m9.figshare.5104873.v1특허: US08822430B2uspto-grants-2014_09