반응 #157505

ord-d8911cbbd70944899fe4ee5caf60b0ba

반응 조건

상세 조건
See reaction.notes.procedure_details.

후처리

  1. 1
    기타quenched by dropwise addition of MeOH
  2. 2
    기타removed from the cooling bath
  3. 3
    workup.STIRRINGafter stirring 30 min at room temperature the layers
  4. 4
    기타were separated
  5. 5
    추출The aqueous layer was extracted with CH2Cl2 (×2)
  6. 6
    세척combined organics were washed (water, brine)
  7. 7
    건조dried over Na2SO4
  8. 8
    농축concentrated in vacuo
  9. 9
    온도the solution was heated
  10. 10
    온도under reflux for 2 h
  11. 11
    기타to remove water
  12. 12
    온도Upon cooling
  13. 13
    workup.ADDITIONthe mixture was diluted with <solvent>
  14. 14
    세척washed (water, brine)
  15. 15
    건조dried over Na2SO4
  16. 16
    농축concentrated in vacuo
  17. 17
    기타The residue was purified by flash chromatography (EtOAc/hexanes)

실험 절차

To a solution of 4-iodo-2-(trifluoromethyl)benzonitrile (1.89 g; 6.38 mmol, Note 1) in CH2Cl2 (15 mL) at −40° C. was added DIBAL-H (9.6 mL of a 1.0M solution in CH2Cl2; 9.6 mmol), dropwise over 5 min. The mixture was stirred 30 min, quenched by dropwise addition of MeOH and removed from the cooling bath. To the still-cold mixture was slowly added HCl (10 mL of a 6M solution), and after stirring 30 min at room temperature the layers were separated. The aqueous layer was extracted with CH2Cl2 (×2), combined organics were washed (water, brine), dried over Na2SO4 and concentrated in vacuo. The residue was dissolved in PhH (15 mL), along with TsOH.H2O (0.12 g; 0.64 mmol) and ethylene glycol (3.5 mL; 63 mmol), and the solution was heated under reflux for 2 h using a Dean-Stark trap to remove water. Upon cooling, the mixture was diluted with <solvent>, washed (water, brine), dried over Na2SO4, and concentrated in vacuo. The residue was purified by flash chromatography (EtOAc/hexanes), affording the title compound as a pale yellow oil. 1H NMR (400 MHz, CDCl3) δ ppm 4.00-4.11 (m, 2 H), 4.11-4.24 (m, 2 H), 6.06 (s, 1 H), 7.54 (d, J=8.4 Hz, 1 H), 7.93 (d, J=8.4 Hz, 1 H), 7.99 (s, 1 H).

출처

DOI: 10.6084/m9.figshare.5104873.v1특허: US08822518B2uspto-grants-2014_09