Reaction #12013

Reaction equation

water

ethyl acetate

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

intermediate b

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

sodium trifluoroacetate

→

desired compound

Yield 27.7%

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

Yield 27.7%

Solvents

1-methyl-2-pyrrolidone

Conditions

Workup

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

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%).

Source