反应详情

To a mixture of 5.9 g (26.1 mmol) of the above 2-hydroxy-4-methyl-2-trifluoromethylpent-4-enoic acid ethyl ester in 30 mL of 4-fluoroanisole was added 5.2 g (39.4 mmol) of aluminum chloride in several portions. The mixture became exothermic and turned black with the first addition and was cooled with an ice-water bath. The mixture was stirred for 3 days and was then poured into 200 mL of ice-cold 1 N aqueous HCl and extracted with three 150 mL portions of EtOAc. The combined organic layers were washed with 50 mL of 1 N aqueous hydrochloric acid, three 50 mL portions of brine, dried over magnesium sulfate, filtered, and concentrated in vacuo. The crude residue was purified by silica gel chromatography eluting with EtOAc-hexanes (1:9, then 2:8, then 3:7, then 4:6) to afford 6.6 g (71%) of 4-(5-fluoro-2-methoxyphenyl)-2-hydroxy-4-methyl-2-trifluoromethylpentanoic acid ethyl ester.

1. additionturned black with the first addition
2. temperaturewas cooled with an ice-water bath
3. extractionextracted with three 150 mL portions of EtOAc
4. washThe combined organic layers were washed with 50 mL of 1 N aqueous hydrochloric acid, three 50 mL portions of brine
5. dry with materialdried over magnesium sulfate
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customThe crude residue was purified by silica gel chromatography
9. washeluting with EtOAc-hexanes (1:9