Dichloromethane → 1-(diphenylmethyl)-7-fluoro-3-hydroxy-3-(7-hydroxy-2,3-dihydro-1,4-benzodioxin-6-yl)-1,3-dihydro-2H-indol-2-one

温度

0 °C

To a cooled (0° C.) suspension of 2,3-dihydro-1,4-benzodioxin-6-ol (0.47 g, 3.0 mmol) in anhydrous tetrahydrofuran (12 mL) was added isopropylmagnesium chloride (2 M solution in tetrahydrofuran, 1.7 mL, 3.3 mmol). The reaction mixture was stirred at 0° C. for 1 h, and 7-fluoro-1-(diphenylmethyl)-1H-indole-2,3-dione (1.0 g, 3.0 mmol) and anhydrous dichloromethane (10 mL) were added. The reaction mixture was allowed to stir for 19 h at ambient temperature. The reaction mixture was concentrated in vacuo and was diluted with saturated aqueous ammonium chloride (30 mL) and ethyl acetate (30 mL). The phases were separated and the aqueous phase was extracted with ethyl acetate (2×50 mL). The combined organic extracts were washed with brine (100 mL), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The crude product was purified by column chromatography and eluted with a 8% to 66% gradient of ethyl acetate in hexanes to afford 1-(diphenylmethyl)-7-fluoro-3-hydroxy-3-(7-hydroxy-2,3-dihydro-1,4-benzodioxin-6-yl)-1,3-dihydro-2H-indol-2-one (1.22 g, 84%) as an off-white solid: MS (ES+) m/z 475.0 (M−17).

1. temperatureTo a cooled
2. stirringto stir for 19 h at ambient temperature
3. concentrationThe reaction mixture was concentrated in vacuo
4. additionwas diluted with saturated aqueous ammonium chloride (30 mL) and ethyl acetate (30 mL)
5. customThe phases were separated
6. extractionthe aqueous phase was extracted with ethyl acetate (2×50 mL)
7. washThe combined organic extracts were washed with brine (100 mL)
8. dry with materialdried over anhydrous sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. customThe crude product was purified by column chromatography
12. washeluted with a 8% to 66% gradient of ethyl acetate in hexanes

ORDレコード

ord-215dc75419bf484f9c1a9a35059d6350

出典データセット

uspto-grants-2012_09

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08263606B2