Reaction #12014

Reaction equation

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

Yield 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

Yield 35.2%

Solvents

ethyl acetate

water

tetrahydrofuran

tetrahydrofuran

Conditions

Workup

1. 1
   Temperaturewas heated
2. 2
   Temperatureto reflux for 2 h
3. 3
   workup.ADDITIONwas added
4. 4
   TemperatureThe mixture was heated
5. 5
   Temperatureto reflux for 16 h
6. 6
   Temperaturethen cooled to room temperature
7. 7
   Otherthe phases were separated
8. 8
   ExtractionThe aqueous phase was extracted three times with ethyl acetate
9. 9
   Washthe combined organic layers were washed with 1M aqueous sodium hydroxide solution and brine
10. 10
    Dryingdried over magnesium sulfate
11. 11
    Filtrationfiltered
12. 12
    Otherevaporated
13. 13
    OtherThe residue was purified by chromatography on silica gel (0.032–0.063 mm) with n-hexane as eluant

Procedure

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%).

Source