Sodium Iodide → HCID 22116117, compound

Temperature

-75 °C

5-Fluoro-1,3-dihydro-2H-indol-2-one (2.4 g, 15.9 mmol) (prepared according to the method of Clark et al., Synthesis (1991) 871) was dissolved in freshly distilled tetrahydrofuran with tetramethylethylenediamine (3.7 g, 31.9 mmol) and was cooled to -75° C. under nitrogen. n-Butyllithium (2.4 equivalents) was added and the mixture was stirred at -75° C. for 40 minutes. Iodomethane (9 g, 63 mmol) was added and the mixture was allowed to warm to room temperature. After two hours' stirring at this temperature, water (5 ml) was added and the mixture was concentrated under reduced pressure, the resulting oil was taken up in dichloromethane, washed with dilute hydrochloric acid, dried (MgSO4), filtered and concentrated to dry under reduced pressure to give a yellow oil. This oil was dissolved in N-methylpyrrolidone and stirred at room temperature under nitrogen. Sodium hydride (0.625 g, 15.6 mmol) was added and the mixture was stirred until gas evolution ceased. 2-(2-Chloroethoxy)tetrahydro-2H-pyran (2.5 g, 15 mmol) and sodium iodide (0.1 g, 0.66 mmol) was added and the mixture was warmed to 75° C. for 15 hours. Water was added and the mixture was concentrated under reduced pressure. The residue was taken up in ethyl acetate, washed (×3) with water, dried (MgSO4), filtered and concentrated under reduced pressure. The resulting oil was taken up in methanol, para toluenesulphonic acid (0.1 g, 0.5 mmol) was added and the mixture was stirred at room temperature for 12 h. The mixture was concentrated under reduced pressure, taken up in ethyl acetate, washed (×3) with aqueous sodium hydrogen carbonate solution dried (MgSO4), filtered and concentrated under reduced pressure. The resulting oil was purified by column chromatography on silica gel, (eluent hexane/ethyl acetate) to give 5-fluoro-1-(2-hydroxy-1-ethyl)-1,3-dihydro-2H-indol-2-one as a yellow oil. MS shows 224 (MH+) base peak and 241 (M+NH4)

1. customaccording to the method of Clark et al., Synthesis (1991) 871)
2. temperatureto warm to room temperature
3. additionwas added
4. concentrationthe mixture was concentrated under reduced pressure
5. washwashed with dilute hydrochloric acid
6. dry with materialdried (MgSO4)
7. filtrationfiltered
8. concentrationconcentrated
9. customto dry under reduced pressure
10. customto give a yellow oil
11. stirringstirred at room temperature under nitrogen
12. stirringthe mixture was stirred until gas evolution
13. temperaturethe mixture was warmed to 75° C. for 15 hours
14. concentrationthe mixture was concentrated under reduced pressure
15. washwashed (×3) with water
16. dry with materialdried (MgSO4)
17. filtrationfiltered
18. concentrationconcentrated under reduced pressure
19. stirringthe mixture was stirred at room temperature for 12 h
20. concentrationThe mixture was concentrated under reduced pressure
21. washwashed (×3) with aqueous sodium hydrogen carbonate solution
22. dry with materialdried (MgSO4)
23. filtrationfiltered
24. concentrationconcentrated under reduced pressure
25. customThe resulting oil was purified by column chromatography on silica gel, (eluent hexane/ethyl acetate)

ORD record

ord-22fbb2a41d524447b8cd915f275ad514

Source dataset

uspto-grants-2000_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06166040