Water → (4R,9aR)-4-Methyl-6-trifluoromethyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester

HRID 11917

Reaction equation

HRID 11917 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].[F:23][C:24]([F:29])([F:28])C([O-])=O.[Na+].C(OCC)(=O)C.O>CN1CCCC1=O.[Cu](I)I>[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:24]([F:29])([F:28])[F:23])=[CH:14][CH:13]=3)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 962WaterHCID 8857Ethyl AcetateHCID 517019Sodium TrifluoroacetateHCID 86590113(4R,9aR)-6-bromo-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester2×

Product 1

HCID 69557181(4R,9aR)-4-Methyl-6-trifluoromethyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl esterYield 27.7%

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

To a solution of 0.8 g (2.17 mmol) (4R,9aR)-6-bromo-4-methyl-3,4,9,9a-tetrahydro-1H-2,4a,5-triaza-fluorene-2-carboxylic acid tert-butyl ester (Example 5, intermediate b) in 12 ml 1-methyl-2-pyrrolidone, 2.36 g (17.4 mmol) sodium trifluoroacetate was added. After a solution had formed, 1.65 g (8.7 mmol) copper iodide was added and the reaction mixture was heated to 180 deg C. for 2 h. The mixture was cooled to room temperature, ethyl acetate and water were added and the suspension was filtered through a bed of dicalite speed plus. The phases were separated, the aqueous layer was washed with ethyl acetate and the combined organic phases were washed with brine, dried over magnesium sulfate, filtered and evaporated. The residue was purified by chromatography over silica gel (0.032–0.063 mm) with tert-butyl methyl ether:n-hexane (1:5) as eluant to afford the desired compound as a colorless oil (27.7%).

Workup

  1. customAfter a solution had formed
  2. temperaturethe reaction mixture was heated to 180 deg C
  3. filtrationthe suspension was filtered through a bed of dicalite speed plus
  4. customThe phases were separated
  5. washthe aqueous layer was washed with ethyl acetate
  6. washthe combined organic phases were washed with brine
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. customevaporated
  10. customThe residue was purified by chromatography over silica gel (0.032–0.063 mm) with tert-butyl methyl ether:n-hexane (1:5) as eluant

Sources & evidence

ORD record
ord-b9de31a32fdc4c3f897713ad2e8c473b
Source dataset
uspto-grants-2006_08
Patent number
US07098337B2

Linked notes

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