反应详情

To a solution of 1,4-cyclohexanedione mono-ethylene ketal (8.1 g, 50 mmol) in THF (20 mL) at 10° C. was added a 1 M solution of 4-fluorophenyl magnesium bromide in THF (65 mL, 65 mmol). The resulting mixture was stirred at room temperature for 2 hours before quenching with saturated NH4Cl solution. The solution was extracted with EtOAc 3 times. The combined organic phase was washed with brine, dried over MgSO4 and concentrated. The residue was taken up in toluene (80 mL). To it was added p-toluenesulfonic acid monohydrate (80 mg). The mixture was stirred at reflux with removal of water using a Dean-Stark trap for 2 hours. The resulting solution was washed with saturated NaHCO3 and brine, dried over MgSO4 and concentrated. Purification on silica gel eluting with 5%, 10% and then 15% EtOAc in hexanes provided the title compound (8.8 g, 75%) as a solid. MS calculated (M+H)+ 235. found 235.

1. custombefore quenching with saturated NH4Cl solution
2. extractionThe solution was extracted with EtOAc 3 times
3. washThe combined organic phase was washed with brine
4. dry with materialdried over MgSO4
5. concentrationconcentrated
6. additionTo it was added p-toluenesulfonic acid monohydrate (80 mg)
7. stirringThe mixture was stirred
8. temperatureat reflux with removal of water using a Dean-Stark trap for 2 hours
9. washThe resulting solution was washed with saturated NaHCO3 and brine
10. dry with materialdried over MgSO4
11. concentrationconcentrated
12. customPurification on silica gel eluting with 5%, 10%