反应详情

To a 1 L, 3 necked round bottom flask fitted with a mechanical stirrer was added 3-fluoro-2-iodonitrobenzene (3B Medical, 47.7 g, 179 mmol) and 500 mL absolute ethanol. To this stirred solution was added iron powder (325 mesh, Aldrich, 30 g, 537 mmol) followed by dropwise addition of concentrated HCl (30 mL, 360 mmol). The internal temperature rose from 23 to ˜60° C. over the addition. The flask was fitted with a heating mantle and heated with vigorous stirring for 90 minutes. After cooling to room temperature, 1 N sodium carbonate (300 mL) was added followed by ethyl acetate (200 mL). The mixture was stirred for 30 minutes and then filtered through a pad of celite. The celite was washed with ethyl acetate (3×150 mL). The filtrates were placed in a separatory funnel and the water layer was removed. The organic layer was concentrated under reduced pressure to a volume of ˜200 mL, placed in a separatory funnel, diluted with ethyl acetate (400 mL), washed with brine, dried over sodium sulfate, filtered and concentrated to dryness. The crude product was taken up in ether (300 mL) and made acidic to pH 1 with 2M hydrochloric acid/ether (Aldrich). After 1 hour, the tan solid was isolated by filtration (39.2 g, 80%). The above aqueous layers were extracted with diethyl ether (300 mL), dried over sodium sulfate, combined with the filtrate of the 1st crop, made acidic to pH 1, and isolated as above to give additional tan solid (9.0 g, 18%) for an overall yield of 98%. 1H NMR (300 MHz, CDCl3) δ 7.06 (m, 1H), 6.58 (m, 1H), 6.39 (m, 1H), 5.73 (bm, 1H). MS APCI, m/z=238 (M+H). HPLC 2.19 min.

1. customTo a 1 L, 3 necked round bottom flask fitted with a mechanical stirrer
2. additionThe internal temperature rose from 23 to ˜60° C. over the addition
3. customThe flask was fitted with a heating mantle
4. temperatureheated
5. stirringThe mixture was stirred for 30 minutes
6. filtrationfiltered through a pad of celite
7. washThe celite was washed with ethyl acetate (3×150 mL)
8. customThe filtrates were placed in a separatory funnel
9. customthe water layer was removed
10. concentrationThe organic layer was concentrated under reduced pressure to a volume of ˜200 mL
11. customplaced in a separatory funnel
12. additiondiluted with ethyl acetate (400 mL)
13. washwashed with brine
14. dry with materialdried over sodium sulfate
15. filtrationfiltered
16. concentrationconcentrated to dryness
17. waitAfter 1 hour
18. customthe tan solid was isolated by filtration (39.2 g, 80%)
19. extractionThe above aqueous layers were extracted with diethyl ether (300 mL)
20. dry with materialdried over sodium sulfate
21. customisolated as above