Reacción #2175449

Ecuación de reacción

2,7-di(Boc-amino)fluorene

THF

→

9-formyl-2,7-di(Boc-amino)fluorene

Disolventes

ethyl formate

Condiciones de reacción

Tratamiento posterior

1. 1
   Otro(Note: ethyl formate was stored over K2CO3 to remove formic acid.) The solution
2. 2
   Temperaturawas cooled in an ice bath
3. 3
   workup.ADDITIONsodium hydride 60% in mineral oil was added portion-wise (5.5 eq, 69 mmol, 2.75 g)
4. 4
   Temperaturaheated to 50° C.
5. 5
   Otroafter fitting with a reflux condenser
6. 6
   Temperaturathe reaction was cooled in an ice bath
7. 7
   Otroquenched by the slow addition of deionized water (50 mL)
8. 8
   Extracciónextracted with ethyl acetate (2×400 mL)
9. 9
   SecadoThe combined organic layers were dried with Na2SO4
10. 10
    Filtraciónfiltered
11. 11
    Otroevaporated under reduced pressure
12. 12
    OtroThe crude product (dark brown solid) was purified by flash chromatography
13. 13
    Lavadosilica gel 60 Å step-wise gradient elution 1-5% methanol in chloroform
14. 14
    OtroYield (4.8 g, ˜90%) of a yellow to brown solid

Procedimiento

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, C10 H enol); 6.5 (2 s, 0.1H, NH urethane); 4.1 (m, 0.3H, CH); 1.5 (s, 18H, Boc).

Fuente