Reaktion #12013

Reaktionsgleichung

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

Ausbeute 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

Ausbeute 27.7%

Lösungsmittel

1-methyl-2-pyrrolidone

Reaktionsbedingungen

Aufarbeitung

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

Vorschrift

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%).

Quelle