Reacción #12014

Ecuación de reacción

9-borabicyclo[3.3.1]nonane

propargyl bromide

(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 hydroxide

→

desired product

Rendimiento 35.2%

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

Rendimiento 35.2%

Disolventes

ethyl acetate

water

tetrahydrofuran

tetrahydrofuran

Condiciones de reacción

Tratamiento posterior

1. 1
   Temperaturawas heated
2. 2
   Temperaturato reflux for 2 h
3. 3
   workup.ADDITIONwas added
4. 4
   TemperaturaThe mixture was heated
5. 5
   Temperaturato reflux for 16 h
6. 6
   Temperaturathen cooled to room temperature
7. 7
   Otrothe phases were separated
8. 8
   ExtracciónThe aqueous phase was extracted three times with ethyl acetate
9. 9
   Lavadothe combined organic layers were washed with 1M aqueous sodium hydroxide solution and brine
10. 10
    Secadodried over magnesium sulfate
11. 11
    Filtraciónfiltered
12. 12
    Otroevaporated
13. 13
    OtroThe residue was purified by chromatography on silica gel (0.032–0.063 mm) with n-hexane as eluant

Procedimiento

A suspension of 150.0 mg (1.23 mmol) 9-borabicyclo[3.3.1]nonane and 47 μl (0.62 mmol) propargyl bromide in 1 ml tetrahydrofuran was heated to reflux for 2 h. The mixture was cooled to room temperature then 0.61 ml (1.83 mmol) of a degassed 3M sodium hydroxide solution was added and after 1 h a mixture of 0.20 g (0.54 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) and 19.0 mg tetrakis(triphenylphosphine)palladium in 1 ml tetrahydrofuran was added. The mixture was heated to reflux for 16 h then cooled to room temperature and poured into water and ethyl acetate; the phases were separated. The aqueous phase was extracted three times with ethyl acetate and the combined organic layers were washed with 1M aqueous sodium hydroxide solution and brine, dried over magnesium sulfate, filtered and evaporated. The residue was purified by chromatography on silica gel (0.032–0.063 mm) with n-hexane as eluant to afford the desired product as a colorless oil (35.2%).

Fuente