Reaktion #2175449

Reaktionsgleichung

2,7-di(Boc-amino)fluorene

THF

→

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

Lösungsmittel

ethyl formate

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstige(Note: ethyl formate was stored over K2CO3 to remove formic acid.) The solution
2. 2
   Temperaturwas 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
   Temperaturheated to 50° C.
5. 5
   Sonstigeafter fitting with a reflux condenser
6. 6
   Temperaturthe reaction was cooled in an ice bath
7. 7
   Sonstigequenched by the slow addition of deionized water (50 mL)
8. 8
   Extraktionextracted with ethyl acetate (2×400 mL)
9. 9
   TrocknenThe combined organic layers were dried with Na2SO4
10. 10
    Filtrationfiltered
11. 11
    Sonstigeevaporated under reduced pressure
12. 12
    SonstigeThe crude product (dark brown solid) was purified by flash chromatography
13. 13
    Waschensilica gel 60 Å step-wise gradient elution 1-5% methanol in chloroform
14. 14
    SonstigeYield (4.8 g, ˜90%) of a yellow to brown solid

Vorschrift

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).

Quelle