反应详情

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, 2H), 4.11-4.24 (m, 2H), 6.06 (s, 1H), 7.54 (d, J=8.4 Hz, 1H), 7.93 (d, J=8.4 Hz, 1H), 7.99 (s, 1H).

1. customquenched by dropwise addition of MeOH
2. customremoved from the cooling bath
3. stirringafter stirring 30 min at room temperature the layers
4. customwere separated
5. extractionThe aqueous layer was extracted with CH2Cl2 (×2)
6. washcombined organics were washed (water, brine)
7. dry with materialdried over Na2SO4
8. concentrationconcentrated in vacuo
9. temperaturethe solution was heated
10. temperatureunder reflux for 2 h
11. customto remove water
12. temperatureUpon cooling
13. additionthe mixture was diluted with <solvent>
14. washwashed (water, brine)
15. dry with materialdried over Na2SO4
16. concentrationconcentrated in vacuo
17. customThe residue was purified by flash chromatography (EtOAc/hexanes)