반응 #62222

ord-eb9dccf2d34547d09cb105f0da72ba8f

반응 조건

온도
120°CELSIUS
상세 조건
See reaction.notes.procedure_details.

후처리

  1. 1
    workup.ADDITIONwere added
  2. 2
    농축The reaction mixture was concentrated in vacuo and concentrated hydrochloric acid (36.5%, 25 mL) in isopropanol (15 mL)
  3. 3
    workup.ADDITIONwas added
  4. 4
    온도The reaction mixture was heated at 90° C. for 24 h
  5. 5
    온도After cooling to 23° C.
  6. 6
    workup.ADDITIONaqueous sodium hydroxide (1N) and aqueous sodium bicarbonate were added
  7. 7
    기타to obtain pH=8
  8. 8
    추출The mixture was extracted with methylene chloride
  9. 9
    건조was dried (MgSO4)
  10. 10
    여과was filtered
  11. 11
    농축concentrated in vacuo
  12. 12
    기타The residue was purified by silica gel chromatography with ethyl acetate/hexanes/methanol (80:20:0 to 76:19:5)

실험 절차

Preparation 87 (N-(4-methoxyphenyl)isonicotinamide, 1 g, 4.39 mmol) was dissolved in phosphorous oxychloride (POCl3) (5 mL) then phosphorous pentachloride (913 mg, 4.39 mmol) was added. The mixture was heated at 120° C. for 4 h. The POCl3 was removed in vacuo, aminoacetaldehyde dimethyl acetal (9.5 mL, 87.8 mmol) and isopropanol (10 mL) were added, and the mixture was stirred at 23° C. for ca. 16 h. The reaction mixture was concentrated in vacuo and concentrated hydrochloric acid (36.5%, 25 mL) in isopropanol (15 mL) was added. The reaction mixture was heated at 90° C. for 24 h. After cooling to 23° C., aqueous sodium hydroxide (1N) and aqueous sodium bicarbonate were added to obtain pH=8. The mixture was extracted with methylene chloride, was dried (MgSO4), and was filtered and concentrated in vacuo. The residue was purified by silica gel chromatography with ethyl acetate/hexanes/methanol (80:20:0 to 76:19:5) to afford 811 mg (74% yield) of the title compound; diagnostic 13C NMR signals (100 MHz, CDCl3) δ 160.069, 149.952, 144.142, 137.853, 131.004, 129.882, 127.414, 124.977, 122.195, 115.114, 55.808; MS (AP/Cl) 252.4 (M+H)+.

출처

DOI: 10.6084/m9.figshare.5104873.v1특허: US07429665B2uspto-grants-2008_09