反应详情

Under argon atmosphere 3-(1,3-Dioxo-1,3-dihydro-isoindol-2-yl)-2,2-difluoro-propionic acid, A2 (13.74 g, 53.85 mmol), dissolved in THF (200 mL) was treated with borane-methylsulfide complex (6.3 mL, 5.04 g, 66.6 mmol). After stirring overnight an additional portion of borane-methylsulfide complex (6.0 mL, 4.80 g, 63.43 mmol) was added. When the reaction was complete it was cautiously diluted with water and extracted with ethyl acetate (2×). An ethyl acetate solution prepared from the residue obtained by evaporation of the initial ethyl acetate extractions at 30° C. in vacuo was washed with water, brine (2×), dried (Na2SO4), filtered, and evaporated in vacuo at 30° C. Crude A3 was sonicated in ethyl acetate, and filtered to give pure 2-(2,2-Difluoro-3-hydroxy-propyl)-isoindole-1,3-dione, A3 (7.45 g). Flash chromatography of the liquor residue (Yamazen, 5 L silica gel cartridge, ethyl acetate/hexane gradient) afforded additional pure 2-(2,2-Difluoro-3-hydroxy-propyl)-isoindole-1,3-dione, A3 (1.39 g).

1. additionwas treated with borane-methylsulfide complex (6.3 mL, 5.04 g, 66.6 mmol)
2. additionwas added
3. extractionextracted with ethyl acetate (2×)
4. customAn ethyl acetate solution prepared from the residue
5. washwas washed with water, brine (2×)
6. dry with materialdried (Na2SO4)
7. filtrationfiltered
8. customevaporated in vacuo at 30° C
9. customCrude A3 was sonicated in ethyl acetate
10. filtrationfiltered