Hydrogen Peroxide → (4R,9aR)-7-Hydroxy-4,6-dimethyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester

HRID 1272122Notes

Reaction equation

HRID 1272122 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:20][C@@H:19]([CH3:21])[N:18]2[C@H:10]([CH2:11][C:12]3[C:17]2=[N:16][C:15]([CH3:22])=[C:14](Br)[CH:13]=3)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].B(OC(C)C)(OC(C)C)[O:25]C(C)C.C([Li])(C)(C)C.OO>C(OCC)C.C(O)(=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:20][C@@H:19]([CH3:21])[N:18]2[C@H:10]([CH2:11][C:12]3[C:17]2=[N:16][C:15]([CH3:22])=[C:14]([OH:25])[CH:13]=3)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 784Hydrogen PeroxideHCID 21531Triisopropyl borateHCID 69357585(4R,9aR)-7-Bromo-4,6-dimethyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl esterHCID 178418306HCID 178418306, compound

Product 1

HCID 69358879(4R,9aR)-7-Hydroxy-4,6-dimethyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl esterYield 75.4%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 3283Diethyl EtherSolvent

Procedure

A stirred solution of 5.40 g (14.1 mmol) (4R,9aR)-7-bromo-4,6-dimethyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester in 350 mL diethyl ether was cooled to −100 deg C. and 6.30 mL (5.13 g, 27.7 mmol) triisopropyl borate was added. To this solution, 11.3 mL (16.9 mmol) tert-butyllithium (1.5 M in n-pentane) was added dropwise and the reaction was stirred at this temperature for another 15 min. The reaction was warmed to −75 deg C., stirred for another 15 min., warmed to 0 deg C., stirred again for 15 min. and then 6.85 mL acetic acid (50% in water) and 0.12 g 35% hydrogen peroxide solution were added successively. The cooling bath was removed and the reaction was stirred for 1 h at room temperature. The reaction mixture was extracted with 10% aqueous thiosulfate solution, the organic layer was washed with brine, dried over magnesium sulfate and filtered. The solvent was removed at a rotary evaporator and the residue was purified by column chromatography on silica gel (0.032–0.063 mm) with ethyl acetate:n-hexane (1:1) as eluant to give the compound as a light yellow solid (75.4%).

Workup

  1. temperatureThe reaction was warmed to −75 deg C
  2. stirring, stirred for another 15 min.
  3. temperaturewarmed to 0 deg C
  4. stirring, stirred again for 15 min.
  5. customThe cooling bath was removed
  6. stirringthe reaction was stirred for 1 h at room temperature
  7. extractionThe reaction mixture was extracted with 10% aqueous thiosulfate solution
  8. washthe organic layer was washed with brine
  9. dry with materialdried over magnesium sulfate
  10. filtrationfiltered
  11. customThe solvent was removed at a rotary evaporator
  12. customthe residue was purified by column chromatography on silica gel (0.032–0.063 mm) with ethyl acetate:n-hexane (1:1) as eluant

Sources & evidence

ORD record
ord-467b645d644d40cea999eec69419bc66
Source dataset
uspto-grants-2007_04
Patent number
US07208494B2

Reaction notes

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