反应详情

Purified 2,7-di(Boc-amino)fluorene (5 g, 12.5 mmol) (prepared from step A, above), was dissolved in ethyl formate (50 mL) and anhydrous THF (60 mL) with gentle heating. (Note: ethyl formate was stored over K2CO3 to remove formic acid.) The solution was cooled in an ice bath and sodium hydride 60% in mineral oil was added portion-wise (5.5 eq, 69 mmol, 2.75 g). The reaction was slowly warmed to room temperature and then heated to 50° C. after fitting with a reflux condenser. After two hours, the reaction was cooled in an ice bath and quenched by the slow addition of deionized water (50 mL). The aqueous layer was adjusted to pH 5 with glacial acetic acid and extracted with ethyl acetate (2×400 mL). The combined organic layers were dried with Na2SO4, filtered and evaporated under reduced pressure. The crude product (dark brown solid) was purified by flash chromatography: silica gel 60 Å step-wise gradient elution 1-5% methanol in chloroform. Yield (4.8 g, ˜90%) of a yellow to brown solid, depending on purity. 1H-NMR (d6-DMSO): δ (ppm) 11.0 (s, 0.9H, enol); 9.3 (2 s, 1.9H, NH urethane); 7.2-8.3 (m, Ar, C10H enol); 6.5 (2 s, 0.1H, NH urethane); 4.1 (m, 0.3H, CH); 1.5 (s, 18H, Boc).

1. custom(Note: ethyl formate was stored over K2CO3 to remove formic acid.) The solution
2. temperaturewas cooled in an ice bath
3. additionsodium hydride 60% in mineral oil was added portion-wise (5.5 eq, 69 mmol, 2.75 g)
4. temperatureheated to 50° C.
5. customafter fitting with a reflux condenser
6. temperaturethe reaction was cooled in an ice bath
7. customquenched by the slow addition of deionized water (50 mL)
8. extractionextracted with ethyl acetate (2×400 mL)
9. dry with materialThe combined organic layers were dried with Na2SO4
10. filtrationfiltered
11. customevaporated under reduced pressure
12. customThe crude product (dark brown solid) was purified by flash chromatography
13. washsilica gel 60 Å step-wise gradient elution 1-5% methanol in chloroform
14. customYield (4.8 g, ˜90%) of a yellow to brown solid