반응 #470433

ord-2f160cd5bc0b456187c9c65c4442a668

반응 방정식

Cc1c(N)cccc1Br
3-bromo-2-methyl aniline
CC(=O)[O-].[K+]
potassium acetate
CC(C)CCON=O
isoamyl nitrite
CC(=O)OC(C)=O
acetic anhydride
C1COCCOCCOCCOCCOCCO1
18-Crown-6
Brc1cccc2[nH]ncc12
4-bromo-1H-indazole
수율 40.0%

반응 조건

상세 조건
See reaction.notes.procedure_details.

후처리

  1. 1
    온도The mixture was cooled with ice-water bath
  2. 2
    기타Ice-water bath was then removed
  3. 3
    기타formed
  4. 4
    온도The mixture was then heated
  5. 5
    온도under reflux for 18 hours
  6. 6
    온도to cool
  7. 7
    기타was partitioned between chloroform (3×10 mL) and saturated aqueous sodium hydrogen carbonate (10 mL)
  8. 8
    세척The combined organic extracts were washed with brine (10 mL)
  9. 9
    건조dried over Na2SO4
  10. 10
    여과filtered
  11. 11
    기타evaporated
  12. 12
    기타to give a crude product which
  13. 13
    기타was purified by column chromatography (ethyl acetate in petroleum ether, 10% v/v)

실험 절차

To a solution of 3-bromo-2-methyl aniline (0104) (0.50 g, 2.69 mmol) in chloroform (5 mL) was added potassium acetate (0.28 g, 2.82 mmol). The mixture was cooled with ice-water bath and then acetic anhydride (0.50 mL, 5.37 mmol) was added to it. Ice-water bath was then removed and the resulting mixture was stirred at room temperature for 10 minutes after which time a white gelatinous solid formed. 18-Crown-6 (0.14 g, 0.54 mmol) was then added followed by isoamyl nitrite (0.80 mL, 5.90 mmol). The mixture was then heated under reflux for 18 hours. The reaction mixture was allowed to cool, and was partitioned between chloroform (3×10 mL) and saturated aqueous sodium hydrogen carbonate (10 mL). The combined organic extracts were washed with brine (10 mL), dried over Na2SO4, filtered and evaporated to give a crude product which was purified by column chromatography (ethyl acetate in petroleum ether, 10% v/v) to give 1-(4-bromoindrazol-1-y1)-ethanone (0105) as an orange solid (0.31 g, 49%), and 4-bromo-1H-indazole (0106-3) as a pale orange solid (0.21 g, 40%). Compound 0105: LCMS: 239 [M+1]+; 1H NMR (400 Hz, CDCl3) δ 2.80 (s, 3H), 7.41 (t, J=6.8 Hz, 1H), 7.50 (d, J=6.0 Hz, 1H), 8.15 (s, 1H), 8.40 (d, J=6.8 Hz, 1H). Compound 0106: LCMS: 197 [M+1]+; 1H NMR (400 Hz, CDCl3) δ 7.25 (t, J=6.0 Hz, 1H), 7.34 (d, J=6.4 Hz, 1H), 7.46 (d, J=6.8 Hz, 1H), 8.12 (s, 1H).

출처

DOI: 10.6084/m9.figshare.5104873.v1특허: US08367663B2uspto-grants-2013_02