Tetrahydrofuran → HCID 86609778, compound

HRID 2367867Notes

Reaction equation

HRID 2367867 reaction equation
[C:1]([NH:8][C:9]1[CH:21]=[CH:20][C:19]2[C:18]3[C:13](=[CH:14][C:15]([NH:22][C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])=[CH:16][CH:17]=3)[CH2:12][C:11]=2[CH:10]=1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].C1C[O:33][CH2:32]C1>C(OCC)=O>[CH:32]([CH:12]1[C:11]2[CH:10]=[C:9]([NH:8][C:1]([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2])[CH:21]=[CH:20][C:19]=2[C:18]2[C:13]1=[CH:14][C:15]([NH:22][C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])=[CH:16][CH:17]=2)=[O:33]

Participants

4

Reactant 2

HCID 8028TetrahydrofuranHCID 66910020C,C′-Bis(1,1-dimethylethyl) N,N′-9H-fluorene-2,7-diylbis[carbamate]

Product 1

HCID 86609778HCID 86609778, compound

Reagents, catalysts & solvents 1

HCID 8025Ethyl formateSolvent

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-c97d40a9f372442e9953a7aa965b68b7
Source dataset
uspto-grants-2014_04
Patent number
US08703115B2

Reaction notes

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