Reacción #12013

Ecuación de reacción

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

Rendimiento 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

Rendimiento 27.7%

Disolventes

1-methyl-2-pyrrolidone

Condiciones de reacción

Tratamiento posterior

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

Procedimiento

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%).

Fuente