反应详情

To a solution of 1-bromo-3,5-difluorobenzene (1.0 equiv.) in THF (0.26 M) under Ar was added Mg turnings (1.6 equiv.). A reflux condenser was attached and the solution was submerged in a 90° C. oil bath and refluxed for two hours. The cyclobutanone (1.0 equiv.) was added in THF via syringe. The solution was left stirring at rt under Ar for 5 hrs. The reaction solution was quenched by addition of NH4Cl(sat) and the solution was extracted with EtOAc, washed with NaCl(sat.), dried over MgSO4, filtered, concentrated and purified by ISCO SiO2 chromatography (0-100% EtOAc/n-heptanes gradient) to yield 1-(3,5-difluorophenyl)cyclobutanol in 54% yield. 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 1.69-1.83 (m, 1H), 2.03-2.13 (m, 1H), 2.31-2.43 (m, 2H), 2.45-2.56 (m, 2H), 6.71 (tt, J=8.80, 2.35 Hz, 1H), 6.98-7.07 (m, 2H).

1. customA reflux condenser was attached
2. customwas submerged in a 90° C.
3. temperaturerefluxed for two hours
4. waitThe solution was left
5. customThe reaction solution was quenched by addition of NH4Cl(sat)
6. extractionthe solution was extracted with EtOAc
7. washwashed with NaCl(sat.)
8. dry with materialdried over MgSO4
9. filtrationfiltered
10. concentrationconcentrated
11. custompurified by ISCO SiO2 chromatography (0-100% EtOAc/n-heptanes gradient)