Acetone → (4R,9aR)-6-(1-Hydroxy-1-methyl-ethyl)-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester

HRID 11952Notes

Reaction equation

HRID 11952 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](Br)=[CH:14][CH:13]=3)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([Li])CCC.[CH3:28][C:29]([CH3:31])=[O:30]>O1CCCC1>[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]([C:29]([OH:30])([CH3:31])[CH3:28])=[CH:14][CH:13]=3)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

5

Reactant 3

HCID 180AcetoneHCID 86590113(4R,9aR)-6-bromo-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl esterHCID 178418339Butyllithium

Product 1

HCID 69556786(4R,9aR)-6-(1-Hydroxy-1-methyl-ethyl)-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl esterYield 24.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of 0.30 g (0.81 mmol) (4R,9aR)-6-bromo-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester in 5 ml tetrahydrofuran was cooled to −78 deg C. and treated with 0.61 ml (0.98 mmol) n-butyllithium solution (1.6 M in n-hexane). After 30 min, 80 μL (71 mg, 1.22 mmol) acetone was added. After 30 min, the reaction was quenched with 10% aqueous ammonium chloride and extracted with ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate and filtered. The solvent was removed on a rotary evaporator and the residue was chromatographed on silica gel (0.032–0.063 mm) with ethyl acetate:n-hexane (1:1) as eluant to afford the compound as a light yellow foam (24.4%).

Workup

  1. waitAfter 30 min
  2. customthe reaction was quenched with 10% aqueous ammonium chloride
  3. extractionextracted with ethyl acetate
  4. washThe organic layer was washed with brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. customThe solvent was removed on a rotary evaporator
  8. customthe residue was chromatographed on silica gel (0.032–0.063 mm) with ethyl acetate:n-hexane (1:1) as eluant

Sources & evidence

ORD record
ord-5d4242cceed147e9bf35f669990436be
Source dataset
uspto-grants-2006_08
Patent number
US07098337B2

Reaction notes

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