反应详情

180 mg of the chiral epoxide of example 17 was dissolved in a mixture of 12 ml chloroform and 12 ml of water. 133 mg of sodium-p-fluorobenzenesulfinate and 107 mg of tetrabutylammonium bromide were added. The reaction mixture was heated till reflux and kept at reflux, while stirring vigorously. The reaction was monitored with HPLC. After 4 days at reflux, the starting epoxide was completely converted. The mixture was cooled to room temperature. 10 ml of chloroform was added. The organic layer was washed with 3×20 ml of water, dried (Na2SO4), filtrated and evaporated to dryness. Residue: 226 mg (brown oil). Purification of the residue by column chromatography (Merck silica gel 60; eluens: heptane/ethyl acetate=1/1) afforded R-enantiomer of bicalutamide as a white/yellow solid material. Purified yield: 122 mg (43%). HPLC: 96.3% purity. HPLC (chiral column): 94.7% e.e. 1H and 13C NMR in agreement with R-bicalutamide

1. temperatureThe reaction mixture was heated
2. temperaturetill reflux
3. temperatureat reflux
4. temperatureAfter 4 days at reflux
5. washThe organic layer was washed with 3×20 ml of water
6. dry with materialdried (Na2SO4)
7. filtrationfiltrated
8. customevaporated to dryness
9. customPurification of the residue by column chromatography (Merck silica gel 60; eluens: heptane/ethyl acetate=1/1)