反应详情

To a suspension of magnesium (0.452 g) in tetrahydrofuran (20 mL), 1-bromo-2,4,5-trifluorobenzene (2.2 mL) was added dropwise at 55° C. over 15 minutes, and the reaction solution was stirred at room temperature for 30 minutes. This solution was added dropwise to a solution of (R)-5-oxopyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-ethyl ester (4.0 g) in tetrahydrofuran (25 mL) at −40° C. over 10 minutes, and the reaction solution was stirred at −40° C. to 0° C. for one hour. Water was added to the solution in small portions at 0° C., followed by extraction with ethyl acetate. The extract was washed with brine, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The residue was purified by silica gel column chromatography (heptane-ethyl acetate system) to obtain 4.5 g of the title compound as a colorless oil. The property values of the compound are as follows.

1. additionwas added dropwise at 55° C. over 15 minutes
2. stirringthe reaction solution was stirred at −40° C. to 0° C. for one hour
3. extractionfollowed by extraction with ethyl acetate
4. washThe extract was washed with brine
5. dry with materialdried over anhydrous magnesium sulfate
6. concentrationconcentrated under reduced pressure
7. customThe residue was purified by silica gel column chromatography (heptane-ethyl acetate system)